Table 1 Study characteristics of retrieved studies
From: Current strategies on kidney regeneration using tissue engineering approaches: a systematic review
Author | Year | Source | Sample | Temperature | Primary stage | Decellularization method | Sterilization |
|---|---|---|---|---|---|---|---|
Uzarski [104] | 2023 | 22 male and female Landrace/Yorkshire/Duroc crossbreed pigs | Whole organ | NM | Peracetic acid (PAA) | Triton X-100 for 3 h + SDS0.3% overnight | PBS with PAA 1000 ppm |
Sauter [20] | 2023 | 6 Wistar rat | Whole organ | Room temperature (RT) | Freeze-thaw at -80 °C | DW for 10 min + 1- SDS 0.66% for 30 min 2- SDS 3% for 30 min + DW for 10 min + 1- SDS 0.66% for 30 min 2- SDS 3% for 30 + DW for 60 min | Antibiotic solution for 60 min |
Salti [15] | 2023 | Male Sprague Dawley rats | Kidney slices | RT | Heparin with PBS + PBS + 1- HHP: At 30 °C kidneys were exposed to three different pressures for 10 min. 2- FTC: kidneys stored at -80 °C for 1h then thawed for half an hour at 4 °C 3- UBS: applying ultrasonic generator with a cold bath | Incubated in EDTA 0.025% for 1 h + Triton X-100 2% for 2 h + SDC 2% for 2 h + SDS 0.1% for 15 h | PBS for 10 min ×3 |
Ma [49] | 2023 | Sheep | Kidney slices | RT | Freeze-thaw at -20 °C + PBS | SDS 0.5-1% + PBS Then Frozen at -20 °C Then Freeze-dried for 14-19 h Then Placed in crosslinking agent for 36-48 h Crosslinking agent: EDC (9.585 g/L) + NHS (5.755 g/L) + MES (9.762 g/L) + ethanol (60%) | PBS + Freeze-dry |
Kim [87] | 2023 | Pigs | Whole organ + Kidney slices | NM | Whole organ: Heparin with PBS for 3 h at 10 ml/min Kidney slices: Heparin with PBS + Freeze at -20 °C | Whole organ: Triton X-100 at 10 ml/min for 12 h + SDS at 5 ml/min for 24 h Kidney slices: Thawed + Triton X-100 for 2 h + SDS for 24 h | + Albumin 25% with PBS at 4 °C + PBS ×3 |
Corridon [106] | 2023 | 24 Male Sprague–Dawley rats | Whole organ | NM | Heparin with PBS + PBS | SDS 0.5% for > 6 h + PBS for 24 h | Gamma irradiation 10 Ky |
Ye [6] | 2022 | Male Sprague–Dawley rats | Kidney slices | RT | PBS | Triton X-100 2% with DI water for 24 h + SDS 0.1% | DI water for 24 h + Freeze at -80 °C |
Yang [17] | 2022 | Pig | Kidney slices | RT | DI water + Freeze at −20 ~ −30 ◦C for 10 ~ 14 h + PBS | SDS 0.5-1% for 48-72 h + PBS ×6-10 + Freeze at −20 ~ −30 ◦C for 3~5 h + Freeze-dry for 14-19 h Then, for 36-48 h Crosslink using Ethanol, EDC, NHS, MES + PBS ×5-6 Finally Freeze-dried for 14-19 h | Ethanol 75% + Ultraviolet irradiation |
Yang [11] | 2023 | Sprague–Dawley rats | - | - | Freeze-thaw at -20 ° C and -80 ° C | Cryoprotectants were used in two groups, including A) low (10% dimethyl sulfoxide and 5% trehalose) and B) high concentration (VS55 and VS83) Cryoprotectants | - |
Shahraki [43] | 2022 | Human (8 kidneys) | Kidney slices | 4 °C | PBS ×2 | 1- Triton X-100 1% or SDS 1% in DW + DNase 1 in PBS for 1 h + PBS 2- SDS 0.5% or Triton X-100 1% in DW + PBS for 5 days | DW and PBS for 1 h + Ethanol 70% for 15 min |
Pantic [141] | 2022 | Yorkshire pigs | Whole organ | RT | Heparin with PBS | Triton X-100 1% for 36 h + SDS 0.5% with PBS for 36 h + PBS for 72 h. | PBS + Gamma irradiation (10 kGy) |
Lee [108] | 2022 | Pig | Kidney slices | 4 °C | PBS ×2 | Triton X-100 1% for 1-1.5 weeks. Then Freeze-dried | Sterilized with ethylene oxide gas. To increase solubilization Soaked in Acetic acid (AA) 0.5 M at 80 °C for 5 min |
Kim [129] | 2022 | Pig | Kidney slices | 37 °C | Freeze + DW for 30 min | Triton X-100 0.5% in 1M NaCl for 16 h + DW ×3 for 1 h + DNase for 6-7 h + PBS for 12 h | PAA 0.1% for 1 h + DW + Freeze-dried at -80 °C Finally, being prepared for hydrogel production |
Hsu [9] | 2022 | 7 Rats | Whole organ | - | - | SDS 1% | - |
Geraldine Haeublein [22] | 2022 | 92 Female Wistar rats | Whole organ | 4 °C | Physiologic solution | 1- 2 ml of SDS 0.1% + 10 ml NaCl 2- 2 cc of 0.01% SDS + 10 ml NaCl 3- Sucrose + EDTA with increasing osmolarity pattern | |
Ghorbani [55] | 2022 | New Zealand white rabbits | Whole organ | NM | DW with heparin 0.01% | SDS 1% for 90 h + PBS 1 liter + Triton X-100 2% in DW for 12 h + DW 1 liter | DW with antibiotics for 10 days |
Corridon [105] | 2022 | 20 Sprague Dawley rats | Whole organ | NM | Heparin with PBS | SDS 0.5% for 6 h + PBS for 24 h | Sterilized with gamma irradiation 10 Ky |
Bongolan [35] | 2022 | Male Yorkshire pigs and Human | Kidney slices | RT | - | 1- SDS 0.05% for 24 h 2- SDS 0.075% for 24 h 3- SDS 0.1% for 24 h 4- SDS 1% for 24 h | PBS for 24 h |
Zhou [85] | 2021 | Sprague Dawley rats | Whole organ | NM | Heparin 50 U/ml in PBS 0.01 M for 30 min | Triton X-100 1% for 1.5 h + DI water for 30 min + SDS 0.8% for 2 h + DI water with antibiotics for 2 h | DI water with antibiotics for 7 days |
Zhang [26] | 2021 | 40 Male Sprague Dawley rats | Whole organ | 37 °C | Heparin with PBS | Triton X-100 1% 500 ml + PBS (500 ml) + SDS 0.8% 1000 ml | DI water with antibiotic 2000 ml |
Xie [84] | 2021 | Male Sprague Dawley rats | Whole organ | NM | PBS | Triton X-100 1%/0.1% ammonium hydroxide for 12 h + PBS with antibiotics and DNase 1 0.0025% for 24 h | - |
Taylor [75] | 2021 | Sprague Dawley rats | Whole organ | 25 °C | - | SDS 1% in DI water + DI water + Triton X-100 1% + PBS with antibiotic + DNase 100 U/ml for 4 h + PBS with antibiotic | - |
Sobreiro [119] | 2021 | Pig | Kidney slices | 4 °C | - | SDS 1% + Milli-Q water for 7 days + Triton X-100 1% + Freeze at -80 °C + Then freeze-dried Finally grinder | Sterilized by ethylene oxide |
Shahraki [23] | 2021 | 10 Male Wistar rats | Kidney slices | 4 °C | - | 1- SDS 1% in DW 2- Triton X-100 1% in DW | PBS ×2 + SDS treated scaffolds: DW with PBS for 1 h + Ethanol 70% for 15 min |
Sant [36] | 2021 | Yorkshire breed pigs | Kidney slices | 37 °C | - | First SDS 1% with 0.02% sodium azide + DI water for 5 days + Ribose in various concentrations in PBS for 4 weeks Then DTPA 10 mM and PM 20 mM were added for Advanced glycation end product inhibition | - |
Manalastas [39] | 2021 | Pig | Whole organ | NM | - | First 1- SDS 0.25% 2- SDS 0.625% 3- SDS 1% Then + Triton X-100 | - |
Mallis [19] | 2021 | 50 Female Wistar rats | Whole organ | RT | PBS | First incubation in CHAPS buffer, pH: 7 (8 mM CHAPS, 1 M NaCl and 25 mM EDTA, in PBS 1x) for 12 h Then incubation in SDS buffer, pH:7 (1.8 mM SDS, 1 M NaCl and 25 mM EDTA, in PBS 1x) for 12 h Finally, kidneys were placed in a-minimum medium essentials with PBS 40% for 12 h Whole technique was repeated for two more times | PBS |
Ko [41] | 2021 | Pig | Kidney slices | NM | NM | NM | NM |
Kim [10] | 2021 | Sprague-Dawley rats | Whole organ | - | - | SDS + Triton X-100 for 9 h | Heparin with antibiotic |
Keshvari [24] | 2021 | 12 Male Sprague–Dawley | Whole organ | NM | PBS 0.1 M for 2 h at 2 ml/min | 1- SDS 1% for 4 h + PBS for 2 h 2- SLES 1% for 6 h + PBS for 2 h 3- Control | - |
Corridon [38] | 2021 | Yorkshire pigs | Whole organ | - | - | Triton X-100 1% in DI water for 36 h + SDS 0.5% in PBS for 36 h + PBS for 72 h | PBS + Gamma irradiation 10 kGy |
Ullah [45] | 2020 | Human | Kidney slices | RT | DW at 4 °C for 2 h | SDS 1% for 3 h + DW at 4 °C for 30 min + DNase1 350 IU/ ml in PBS for 2 h at 4 °C + DW at 4 °C for 30 min + PBS with antibiotics for 2 h at 4 °C Finally, Heparitinase-1 solution (Sodium acetate0.1 M, Calcium acetate 10 mM, and heparitinase-110 mU) for 3 h at 37 °C + PBS for 5 min×3 | - |
Tajima [56] | 2020 | 3 Beagle dogs | Whole organ | NM | Freeze at -80 °C + NaCl for 2 h | SDS 0.5% for 6 h + NaCl for 2 h | - |
Sobreiro [40] | 2020 | Pig | Kidney slices | - | - | SDS 1% + Triton X-100 1% | Washed Then Freeze-dried Finally Reduced to powder |
Moradi [54] | 2020 | One Male New Zealand White rabbits | Whole organ | - | PBS 1 liter for 1 h | SDS 2% for 2 days + Triton X-100 for 24 h + PBS for 7 days | 1- Antibiotic solution 2- PAA 3- UV, gamma irradiation |
Hu [16] | 2020 | 30 Sprague–Dawley rats | Whole organ | 4 °C | Heparin 50 U/ml with PBS at 4 ml/min + Frozen at -80 °C for 3 h + Thawed at 4 °C for 6 h | Triton X-100 0.1% for 3 h + SDS 0.5% for 20 min | PBS with antibiotics for 24 h |
Feng [18] | 2020 | Male Sprague-Dawley rats | Whole organ | 20 °C | PSB with EDTA 10 mM for 30 min | Triton X-100 0.3% with 10 mM Tris-Hcl for 24-32 h + DNase 1000 U/L with 10 mM HEPES, 2mM CaCl2, 2mM MgCl2 for 24 h + Saline 0.9% for 2 h + 10 mM EDTA in PBS for 16 h | - |
Zhang [132] | 2019 | 30 Wistar rats | Whole organ | NM | PBS | SDS 0.5% for 6 h | PBS for 24 h |
Ullah [44] | 2019 | 13 Human | Kidney slices | RT | Frozen at -80 °C + DW for 60 min at 4 °C | SDS 0.1% for 1 h + DW for 15 min at 4 °C + DNase1 350 IU/ml for 1 h + DW for 15 min at 4 °C ×3 + PBS with antibiotics for 60 min Then Heparan sulfate proteoglycans (HSPG) and heparin-binding growth factors (HBGFs) were removed to remove HBGFs Finally, Scaffolds were supplemented with VEGF. | - |
Lih [112] | 2019 | Female Yorkshire pigs | Kidney slices | 4 °C | PBS | First Triton X-100 1% with antibiotics + PBS + DNase (30 μg/ml) in PBS for 1 h Then freeze-milled for 3 days Finally, The freeze-milled substance mixed with Mg(OH)2 and PLGA, producing a mixture. | - |
Leuning [95] | 2019 | Human and Lewis rats (Charles River) | Whole organ | For human: UW containing heparin at 0°C for 30 h + PBS with heparin 500 IE/L + SDS with PBS containing antibiotics and DNase for 5 days + DW with antibiotic with DNase for overnight | For rats: SDS 1% in PBS-containing antibiotics + DNase 2500 E for 12 h + DW for 15 min + Triton X-100 1% for 30 min For human: Triton X-100 1% for 1 day | For rats: PBS with antibiotics for 48 h For human: PBS with antibiotic for 5 days | |
Kajbafzadeh [48] | 2019 | 8 Sheep | Whole organ | 10 °C | Saline with heparin and antibiotics | 1- Triton X-100 1% (5 Liter) + SDS 0.5% (20 Liter) + PBS 4 liter 2- SDS 1% (40 Liter) | DW |
Hu [12] | 2019 | Male Sprague-Dawley rats | Whole organ | - | PBS | 1- SDS 2- SDS + Triton X-100 3- Repeated freeze-thaw + Triton X-100 + SDS | - |
Ciampi [88] | 2019 | Sprague-Dawley rats | Whole organ | RT | - | SDS 1% FOR 6 h | DW + PBS with antibiotics for 2 h |
Alnazer [142] | 2019 | 8 Mice | - | - | - | SDS for 24 h + Triton X-100 for 24 h | PBS |
Ali [10] | 2019 | Yorkshire pig | Whole organ | NM | Heparin 10 U/ml with PBS for 15 min at 0.75 L/h | SDS 0.5% in DI water for 36 h + Triton X-100 1% /0.1% ammonium hydroxide for 36 and 24 h, respectively at 5 ml/min + Normal saline for 72 h + DNase 500 ml (0.0025% (w/w) DNase and 10 mM magnesium chloride in 0.1 M PBS) Then freeze-dried and milled, being prepared for further use as a bioink in 3D-printing. | PBS for 1 h |
Zambon [79] | 2018 | Yorkshire pigs | Whole organ | RT | Heparin 10 U/ml with PBS for 15 min at 0.75 liter/ h | 1- SDS 0.5% in PBS for 36 h at 12.5 ml/ min + PBS for 48 h + DNase 500 ml of 0.0025% and 10 Mm MgCl2 in PBS overnight + PBS for 1 h 2- Triton X-100 1% in DI water for 36 h at 5 ml/ min + SDS 0.5% in PBS for 36 h + PBS for 72 h | Gamma irradiation 10 kGy |
Xue [90] | 2018 | Wistar rats | Whole organ | NM | PBS | SDS 0.5% for 8 h at 500 µl/min | PBS with antibiotic for 2 days |
Wang [83] | 2018 | 12 Sprague Dawley rats | Whole organ | Heparin with Saline + PBS for 30 min at 0.4 ml/min | First 1- Triton X-100 for 12 h 2- High hydrostatic pressure (600 MPa) for 30 min + SDS 0.5% 3- SDS 0.5% for 12 h Then Heparin was Immobilized to a decellularized scaffold via collagen-binding peptide. | PBS with antibiotic for 24 h | |
Su [113] | 2018 | Female Yorkshire pig | Kidney slices | RT | Frozen at -80 °C + Thawed + DI water for 1 day | SDS 0.1% for 2 days + DI water for 1 day *Hydrogel was prepared from decellularized ECM | Frozen at -80 °C |
Padalhin [134] | 2018 | Sprague‐Dawley rats | Whole organ | NM | Saline with antibiotics | SDS 1% for 4 h + Triton X-100 for 4 h | DW for 1 h + PBS with antibiotics |
Kajbafzadeh [133] | 2018 | 10 Male Wister rats | NM | NM | NM | Detergent based (NM) | NM |
Hussein [34] | 2018 | Mixed breed adult pigs | Whole organ | NM | PBS with heparin for 30 min | SDS 0.1% in DW + PBS for 8 h | PAA 0.1% for 2 h + PBS for 12 h |
Fedecostante [109] | 2018 | 20 Male Wistar rats | Whole organ | RT | Heparin in HBSS for 15 min at 2ml/min + Frozen at -20 °C | SDS 1% at 2 ml/ min in HBSS for 21 h + HBSS for 30 min + Triton X-100 1% in HBSS for 30 min + HBSS with antibiotics for 48 h at 1 ml/min + DNase1 0.0025% with CaCl2 5mM and MgCl2 5mM in HBSS for 5 h | PAA 0.2% and Ethanol 4% for 10 min + HBSS with antibiotic ×3 |
Bombelli [107] | 2018 | 18 Human (11 Male) | Kidney slices | NM | PBS with antibiotic for 15 min ×2 | Trypsin 0.02% for 1 h + PBS for 15 min ×2 + Tween-20 for 2 h + PBS for 15 min ×2 + SDC 4% for 3 h + PBS for 15 min ×2 + SDS 1% | PBS with antibiotic for 4 h ×2 |
Almelkar [47] | 2018 | Sheeps | Whole organ | NM | Normal saline 500 ml | Day 1: 500 ml of SDS 1% in 2 h at 60 drop/ min. Then perfused for 10 h and kept in SDS 1% overnight. Day 2: SDS 1% at 10 drop/ min for 8 h Day 3: Same as Day 2 Day 4: SDS 1% + Trypsin at 30 drop/ min Day 5: SDS 1% + EDTA 1% at 60 drop/ min Whole procedure repeated 2 cycle. | - |
Uzarski [102] | 2017 | Male Sprague Dawley rats | Whole organ | NM | Frozen at -80 °C + Thawed | Triton X-100 1% + SDS 0.1% | PAA 0.1% and Ethanol 4% for 1 h at 4 ml/min + PBS ×3 |
Sambi [98] | 2017 | Mice | Whole organ and Kidney slices | NM | - | Whole organ: SDS 0.1% at 0.2 and 0.4 ml /min for 12, 24, 48, or 72 h + Triton X-100 0.1% for 1 h + PBS for 24 h 2- Triton X-100 0.1% for 24-72 h 3- SDC 0.4% for 24-72 h +/− 90 U/ml benzonase for 2 h Kidney slices: SDS 0.1% for 24 h at 0.4 ml/min + PBS for 24 h | - |
Remuzzi [92] | 2017 | Male Sprague-Dawley rats | Whole organ | NM | Normal saline with nitroprusside 10-4 M | SDS 1% in DW for 6 h at 0.4 ml/min Prior to cell seedeing, scaffold was perfused with same medium for 2 h. | DW with PBS with antibiotic |
Poornejad [91] | 2017 | 50 Pigs | Whole organ | NM | PBS with heparin + Frozen at -20 °C | SDS 0.5% in DI water for 7 h | DI water for 48 h at 10 ml/min |
He [21] | 2017 | Male Wistar rats | Whole organ | NM | PBS with nitroprusside + PBS for 30 min | 1- SDS 1% for 24, 8, and 4 h 2- SDS 0.125% for 4 and 8 h 3- SDS 0.25% for 4 and 8 h 4- SDS 0.5% for 4 and 8 h 5- SDS 1% for 4 h PBS for 1h at the end of every protocol | PBS with antibiotic for 18 h at 2 ml/min |
Fischer [37] | 2017 | Infant pigs | Kidney slices | 1- 4 °C 2- RT 3- 37 °c | Frozen at -20 °C for 24 h + Thawed + DMEM with antibiotic for 5 min ×3 + DW for 24 h | 1- SDS 1% + DNase I 350 IU ml-1 in DMEM for 18 h 2- Triton X-100 1% + DNase I 350 IU ml-1 in DMEM for 18 h 3- SDC 1% + DNase I 350 IU ml-1 in DMEM for 18 h Each for 7-10 days | DMEM with antibiotic for 18 h |
Chani [72] | 2017 | 12 Female Sprague-Dawley rats | Whole organ | RT | First Saline with heparin Then 1- Control 2- Decellularized after nephrectomy (Without cryopreservation) 3- Decellularized 3 months after nephrectomy (cryopreservation) | SDS 1% in DW for 48 h + DNase I at 0.2 mg/ ml and MgCl2 10 mM in PBS for 16 h + PBS | PBS with antibiotic and DNase I for 24 h at 4 °C + PBS with antibiotic for 24 h + PBS with UV for 1-2 h + DMEM with UV for 1 h |
Wang [121] | 2016 | 60 Male Sprague-Dawley | Whole organ | NM | Heparin 50 U/ml in PBS 0.01 M for 30 min | Triton X-100 0.1% for 3 h + DI water for 30 min + SDS 0.8% for 3 h + DI water with antibiotic for 24 h | DI water with antibiotics at 4 °C for < 7 days |
Poornejad [33] | 2016 | Yorkshire swine | Whole organ and Kidney slices | RT | PBS with heparin + Frozen at -20 °C + Thawed slowly overnight at 4 °C + DI water for 15 min ×5 | A- For renal slices: 1- Triton X-100 3% 2- SDS 1% 3- Trypsin/ EDTA 0.05% 4- PAA 1% All repeated five times B- For whole kidney: Perfusion with NaOH 0.1 N with gradual increase in perfusion rate from 10 to 40 ml/ min for 7 h. + DI water for 2 days | Ethanol 70% with antibiotics for 1 h + DI water |
Poornejad [80] | 2016 | Yorkshire swine | Whole organ | RT | PBS with heparin 10 U/ml + Frozen at -20 °C + Thawed slowly at RT | SDS 0.5% for 5-7 h + DI water for 2 days | Slices were soaked in 50 ml of solutions and stirred for 0.5, 1, 2, 3, 4, and 5 h: 1- Gamma irradiation 1-10 kGy 2- Ethanol 70% in DI water 3- PAA 0.2% in 1M NaCl in dilute AA 4- PAA 0.2% in ethanol 4% in DI water |
Poornejad [32] | 2016 | 20 Yorkshire swine | Whole organ | RT | PBS with heparin + Frozen at -20 °C + Thawed at 4 °C | 1- Hypertonic solution (0.5 M NaCl) for 30 min + 0.5% SDS for 30 min + DI water for 30 min 2- SDS 0.5% for 30 min | DI water for 2 days + Ethanol 70% |
Nagao [115] | 2016 | Human | Kidney slices | NM | - | First SDS 1% for 5 days + DW for 5 days + Frozen at -20 °C Then Decellularized scaffold was used to mix with collagen I and to subsequently produce hydrogel. | - |
Mei [114] | 2016 | Sprague Dawley | Whole organ | PBS 0.01 M with heparin U/ml for 30 min | Triton X-100 0.1% for 3 h + DI water for 3 h + SDS 0.8% for 3 h | DI water with antibiotics for 24 h | |
Lih [111] | 2016 | Female Yorkshire pigs | Kidney slices | 4 °C | PBS | Triton X-100 1% with antibiotics for 14 days (200 rpm) + DNase (30 µg/mL) in PBS for 1 h + PBS Then freeze milling was conducted to produce ECM powder. Finally, ECM at different concentrations (0.2%, 1%, 5%, and 10%) mixed with PLGA to develop a mixed scaffold. | Ethylene oxide |
Du [96] | 2016 | Mice | Whole organ | - | PBS | SDS 1% in DI water for 3 h (first 30 min at 3 ml/ min, remaining time at 0.5 ml/ min) + DI water for 15 min at 0.5 ml/min + Triton X-100 1% in DI water for 16 h at 0.1 ml/ min + DMEM | - |
Abolbashari [103] | 2016 | 10 Female Yorkshire pigs | Whole organ | NM | Heparin | SDS 0.5% in PBS for 36 h + PBS + DNase 0.0025% + PBS | Gamma irradiation at 1 MRad |
Zhang [120] | 2015 | 90 Sprague Dawley rats | Whole organ | 37 °C | PBS with heparin 10 U/ml | Triton X-100 0.1% (1000 ml) + DI water 200 ml + SDS 0.8% (2000 ml) + DI water (5000 ml) with antibiotics and heparin | X – Gray at 2 KC Gray with PBS for 4 min |
Wang [31] | 2015 | Bama miniature pigs | Whole organ | RT | NaCl, KCl, HEPES, and EGTA + PBS ×2 + Frozen at -20 °C + Thawed at RT | DW for 3 h + Freeze overnight and thaw + DW for 3 h + 1- SDS 1% 2- Triton X-100 1% 3- PAA 4- SDC Each for 18 h + PBS for 3 h | - |
Uzarski [100] | 2015 | Sprague Dawley rat | Whole organ | RT | PBS at 4 °C + Frozen at -20 °C + Thawed at RT + PBS | ROH20 at 5 ml/min for 1:40' (500 ml) + Triton X-100 1% (1000 ml) at 5 ml/ min for 3:20' + Triton X-100 1% (1000 ml) at 5 ml/ min for 16:40' + SDS 0.1% (1000 ml) at 5 ml/ min for 3:20' + ROH20 at 5 ml/min for 1:40' (500 ml) | PAA 0.1%, Ethanol 4% at 5 ml/min for 1 h |
Uzarski [101] | 2015 | Male Sprague Dawley rats | Whole organ | RT | PBS + Frozen at -20 °C + Thawed at RT | ROH20 at 5 ml/min for 1:40' (500 ml) + Triton X-100 1% (1000 ml) at 5 ml/ min for 3:20' + Triton X-100 1% (1000 ml) at 5 ml/ min for 16:40' + SDS 0.1% (1000 ml) at 5 ml/ min for 3:20' + ROH20 at 5 ml/min for 1:40' (500 ml) | PAA 0.1%, Ethanol 4% at 5 ml/min for 1 h + PBS for 1 h ×3 |
Rafighdoust [82] | 2015 | BALB/ c mice | Whole organ | - | Normal saline + Frozen at -4 °C + Thawed + Soaked in liquid Nitrogen for 2 min + DW for 5 min for rapid thawing + PBS at 37 °C | SDS 1% for 48 h + PBS for 24 h Finally, The scaffold material was treated with an impregnation of Chondroitin sulfate. | Sterilized via Ethanol 70% for 30 min + DW and PBS for 1 h |
Poornejad [71] | 2015 | Pigs | Whole organ | - | PBS with heparin In group 1 undergoing Freeze-thaw: The kidneys underwent -20 °C for a duration of 24 h, followed by another freezing phase at -80 °C for 12 h. Subsequently, they were kept at a temperature of -20 °C for 24 h, and ultimately thawed at +4 °C. | SDS 0.5% for 7 h + DI water for 2 days | Sterilized with Ethanol 70% for 2 h |
Peloso [7] | 2015 | 40 Human | Whole organ | NM | PBS for 12 h at 12 ml/min | SDS 0.5% for 48 h + DNase for 6 h (6 ml/ min) + PBS for 5 days (6 ml/ min) | - |
Peloso [78] | 2015 | 33 Male Lewis rats | Whole organ | RT | Saline with heparin 100 ml/min at 4 °C | Triton X-100 1% (100 ml) + PBS (50 ml) at 50 ml/min + SDS 1% (100 ml) + PBS (50 ml) at 50 ml/min | - |
Ofenbauer [99] | 2015 | Female NMRI mice | Kidney slices | NM | PBS for 1 h | First, 30 ml Hypotonic solution of 10 mM Tris/HCl + 5 mM EDTA in DI water with antibiotics Then 1- 90 h of hypotonic solution ×4 + SDS 1% for 48 h + PBS with antibiotic for 72 h ×2 2- 70 h of hypotonic solution with protease inhibitors ×3 + SDS 1% for 2.5 h + SDS 0.1% for 70 h + PBS with antibiotic for 50 h + FBS 15% for 90 h + PBS with antibiotic for 72 h ×2 3- 70 h of hypotonic solution with protease inhibitors ×3 + 70 h PEG solution 1000 1% + SDS 1% for 2.5 h + SDS 0.1% for 70 h + PBS with antibiotic for 50 h + FBS 15% for 90 h + PBS with antibiotic for 72 h ×2 | - |
Liu [74] | 2015 | 20 Male Sprague-Dawley rats | Whole organ | NM | PBS with heparin for 30 min | Triton X-100 3% for 30 min + DI water for 15 min + 5 Mm CaCl2 and 5 Mm MgCl2 for 30 min + DI water for 15 min + Triton X-100 3% for 30 min + DI water for 15 min + SDS 1% for 12 h + DI water for 15 min | PBS with antibiotic for 48 h |
Guan [27] | 2015 | Male Wistar rats | Whole organ | NM | - | 0.01 M PBS for 15 min + SDS 0.5% for 4 h + PBS for 24 h | - |
Guan [30] | 2015 | 40 Pigs | Whole organ | RT | PBS with heparin | DW for 2 h + SDS 1% for 28 h + Triton X-100 1% for 2 h | PBS for 4 days |
Choi [77] | 2015 | Female Yorkshire pig | Kidney slices | 4 °C | PBS ×2 | For 10-14 days 1- Triton X-100 1% in DW with antibiotic 2- SDS 1% in DW with antibiotic Finally, DNase 30 µg/ml in PBS for 1 h + PBS | Gradient Ethanol |
Caralt [25] | 2015 | Male Sprague Dawley rats | Whole organ | NM | 500 ml of DI water for 1:40' | 1- Triton X-100 1% (1000 ml) for 3:20' + Triton X-100 1% (1000 ml) for 16:40' + Triton X-100 1% (1000 ml) for 3:20' 2- Triton X-100 1% (1000 ml) for 3:20' + Triton X-100 1% (1000 ml) for 16:40' + SDS 0.1% (1000 ml) for 3:20' 3- Trypsin 0.02% + EGTA 0.05% for 2 h + Triton X-100 1% (1000 ml) for 16:40' + Triton X-100 1% (1000 ml) for 3:20' | DI water for 1:40' |
Batchelder [53] | 2015 | Rhesusmonkeys | Whole organ and Kidney slices | RT | For whole kidneys: Heparin 100 USP/ml in PBS for 15 min at 1ml min | For whole kidneys: SDS 1% in DW at 5ml/ h for 3-4 days + PBS with antibiotic for 72-96 h For kidney slices: SDS 1% for 5-8 days + PBS with antibiotic for 24 h ×3 + 70% ethanol for 24 h + PBS with antibiotic for 24 h | - |
Yu [135] | 2014 | Male Sprague Dawley rats | Whole organ | NM | Heparin 50 U/ml in PBS 0.01 M for 30 min | Triton X-100 0.1% for 3 h + DI water for 30 min + SDS 0.8% for 3 h + DI water with antibiotic for 24 h | DI water with antibiotics at 4 °C for < 7 days |
Vishwakarma [46] | 2014 | Male Goats | Whole organ | 37 °C | Antibiotic containing saline with heparin 50 U/ ml for 30 min | SDS 0.1% for 30 min + SDS 0.5% for 48 h + SDS 0.1% for 24 h + Triton X-100 0.1% for 30 min + CaCl2 with MgSO4 5mM + DNase I 0.0025% | DI water for 15 min + PBS with antibiotic for 48 h |
Ko [81] | 2014 | Pigs | Whole organ | - | - | Heparin + SDS 0.5% in PBS for 36 h + PBS + DNase 0.0025% for 12 h + PBS | Sterilized via gamma radiation 1 MRad |
Finesilver [97] | 2014 | Lewis rats | Kidney slices | NM | NaCl 1M for 20 min ×3 + DDW for 5 min × 2 | Triton X-100 0.5% for 30 min × 2 + DDW for 20 min × 3 | PBS with antibiotic overnight |
Chae [29] | 2014 | Female Yorkshire pigs | Kidney slices | 4 °C | PBS | 1- SDS 1% for 3-4 week 2- Triton X-100 1% for 3-4 week | Freeze-dried at -80 °C + Ethylene oxide gas |
Bonandrini [76] | 2014 | 24 Male Sprague-Dawley rats | Whole organ | RT | Saline with nitroprusside | SDS 1% in PBS for 17 h | DW |
Song [89] | 2013 | 68 Male Sprague-Dawley rats | Whole organ | NM | Heparin with PBS for 15 min | SDS 1% for 12 h with DI water + DI water for 15 min + Triton X-100 1% for 30 min in DI water | PBS with antibiotic for 96 h |
Orlando [42] | 2013 | 10 Human | Whole organ | NM | DW for 12 h | SDS 0.5% for 48 h | PBS for 5 days (6 ml/ min) |
O’Neill [94] | 2013 | Yorkshire pigs | Kidney slices | NM | Frozen at -80 °C for > 24 h + Thawed + PBS for 15 min ×2 | Trypsin 0.02% for 2 h + PBS for 15 min ×2 + Tween 20 3% for 2 h + PBS for 15 min ×2 + SDC 4% for 2 h + Washed in PBS for 15 min ×2 | PAA 0.1% for 1 h with PBS and DW |
Nakayama [52] | 2013 | Three Rhesus monkeys (Macaca mulatta) | Kidney slices | NM | PBS | SDS 1% with DW | PBS and antibiotic for 0-2 months + Ethanol 70% in Super-Q water |
Sullivan [73] | 2012 | Yorkshire pigs | Whole organ | NM | Heparin 10 U/ ml with PBS for 15 min | For 36 h: 1- SDS 0.5% in PBS + SDS 0.25% in PBS 2- 1% Triton X-100/0.1% Ammonium Hydroxide in PBS Finally, PBS for 48 h + DNase 0.0025% and 10 mM MgCl2 overnight + PBS for 1 h | PBS and Gamma irradiation 10 kGy |
Ross [93] | 2012 | Male Sprague-Dawley rats | Whole organ | NM | Saline with nitroprusside and heparin | Triton X-100 + SDS + CaCl2 with MgSO4 each at 5mM + D Nase 0.0025% + 1M NaCl with DI water | - |
Park [143] | 2012 | Male Sprague-Dawley rats | Whole organ | NM | PBS | SDS 1% for 4 h in PBS | PBS |
Orlando [28] | 2012 | Female Yorkshire pigs | Whole organ | RT | Saline | DW for 12 h + SDS for 48 h | PBS for 5 days at 6 ml/ min |
Nakayama [51] | 2011 | 21 Rhesus monkeys (Macaca mulatta) | Kidney slices | 4 °C | PBS ×2 | SDS 1% in DW for 7-10 days | PBS + Ethanol 70% in Super-Q water + PBS with antibiotic for 48 h |
Nakayama [50] | 2010 | 34 Rhesus monkeys (Macaca mulatta) | Kidney slices | 4 or 37 °C | PBS ×2 | 1- SDS 1% in DW for 7-10 days 2- Triton X-100 1% in DW for 7-10 days | PBS + Ethanol 70% in Super-Q water + PBS with antibiotic for 24 h at 4 °C |
Ross [13] | 2009 | Male Sprague-Dawley rats | Whole organ | - | Saline with nitroprusside | For 5 days: 1- Triton X-100 with gradual increase in concentration (0.5, 3, 6 and 10%) + SDC 4% 2- Triton X-100 3% + DNase + Triton X-100 3% + SDS 4% Common protocol: CaCl2 with MgSO4 each at 5mM + 1M NaCl + DI water + DNase I 0.0025% in in 50 mM sodium acetate, 10 mM MgCl2, and 100 mM NaCl + NaN3 0.05% | - |
Liu [14] | 2009 | Wistar rats | Whole organ | NM | Heparin with PBS | SDS 1% + DI water + Triton X-100 1% | PBS with antibiotic |
Author | Year | Technique | Cell type | Seeding rout | Aim | Transplantation/ implantation | Findings |
|---|---|---|---|---|---|---|---|
Uzarski [104] | 2023 | Perfusion (constant pressure of artery: 60 mmHg, vein: 40 mmHg) During the PAA and PBS stages, the perfusion was alternated at evenly spaced intervals between the renal artery, vein, and ureter | Human umbilical vein endothelial cells (HUVEC) | First through Artery, then Vein | To determine a threshold glucose consumption rate (GCR) that could be utilized to predict the compatibility and performance of decellularized kidney grafts that were recellularized with HUVECs. | Nine regenerated kidneys were transplanted into adult pigs. | GCR was shown to be a good variable for evaluating biocompatibility and performance of regenerated kidneys. The minimum threshold for GCR was found to be 20mg/h. At days with peak GCR, almost complete endothelial coverage was achieved. |
Sauter [20] | 2023 | Perfusion (constant pressure: 100 mmHg) Through Artery | Human endothelial cells EA. hy 926 1- One kidney in group 1 was reseeded with 20 million cells and two were reseeded with 40 million cells 2- Kidneys of group 2 reseeded with 20 million cells Procedures in both groups were repeated twice | First through Artery, then Vein | To Investigate how two different concentrations of SDS can influence the adhesion and growth of human endothelial cells in an acellular kidney scaffold. | - | Gentle decellularization of kidneys with lower concentrations of SDS culminated in better outcomes and biocompatibility following recellularization. |
Salti [15] | 2023 | Immersion/ agitation | - | - | Explore the impact of various physical treatment techniques on the efficiency of decellularization. | - | Combining the physical FTC method with a chemical technique for decellularization yielded the best outcomes. |
Ma [49] | 2023 | Freeze-dry | Adipose tissue stem cells (ADSCs) | - | To compare and evaluate the impact of crosslinking on outcomes of decellularization. | - | While the molecular structure of the kidneys remained untouched, crosslinking provided biocompatible scaffolds with significant enhancement in mechanical properties. |
Kim [87] | 2023 | Whole organ: Perfusion Kidney slices: Immersion/ agitation | - | 2 × 104 cells were seeded on a rotating culture plus an albumin coat. | To evaluate the effectiveness of recellularization by utilizing the roller bottle technique to modify the surface of the albumin coating. | - | Using a rotator for the recellularization of scaffolds led to better cellular penetration. Using albumin-coated scaffolds prevented blood clot development and enhanced cell proliferation. Therefore, combining dynamic culture and an albumin coat might be an efficient technique. |
Corridon [106] | 2023 | Perfusion (4 ml/min) Through Artery | - | - | To assess the impact of in vivo blood flow on the decellularized scaffolds post-transplantation using intravital microscopy. | Orthotropic transplantation was performed in autologous and allogenic patterns. | Using intravital microscopy provides important information regarding angiogenesis and longevity of the transplanted bio artificial kidney. |
Ye [6] | 2022 | Immersion/ agitation | PC-12 cells | - | To compare Rat decellularized kidney with decellularized peripheral nerve, regarding the presence of various components and growth factors in kidney scaffold. | - | Decellularized kidneys had the potential for nerve repair and regeneration while expressing growth factors, including VEGF and HGF |
Yang [17] | 2022 | Immersion/ agitation + Freeze-drying | Human breast cancer MCF-7 cells and Human ADSCs | - | To study the impact of a secondary microstructure on tumor progression and cell adhesion. The goal is to create a platform that has increased biocompatibility for drug screening and basic cancer research. | - | Nanostructures in the scaffold are vital for cell adhesion, proliferation, and differentiation. By providing more attachment sites for cells, the pig kidney scaffold enhances cell adhesion, proliferation, physiological activities, and the creation of tumor models. |
Yang [11] | 2023 | - | - | To assess the impact of a freeze-thaw procedure and cryoprotectants on the architecture of decellularized scaffolds. | - | Vascular integrity was best preserved at -20 °C temperature. Low-concentration cryoprotectants best achieve the balance between vascular integrity preservation and decellularization. | |
Shahraki [43] | 2022 | Immersion/ agitation | hAd-MSCs | - | To establish a successful technique for producing kidney scaffolds that maintain the requisite matrix architecture essential for the proliferation and differentiation of stem cells into renal cells. | - | Triton X-100 yielded better results with adequate cell adhesion and proliferation. Endothelial and epithelial differentiation was successfully achieved following the detection of their markers, including PECAM-1, PAX2, and E-CDH. |
Pantic [141] | 2022 | Perfusion (5ml/min) Through Artery | - | Continuous blood perfusion was conducted through the renal artery at 200 ml/min rate for 24 h | To utilize a computational algorithm called gray-level co-occurrence matrix to apply imaging methods for analyzing the vascular architecture and parenchymal damage resulting from hypo perfusion in decellularized porcine specimens. | - | GLCM might be an effective standard imaging method for more accurate micro/ macro vasculature integrity assessment. |
Lee [108] | 2022 | Immersion/ agitation + freeze-dry | Human renal proximal tubular epithelial (RPTE) | - | To verify renal decellularized ECM efficiency and cell responses as hydrogel, coat, and scaffold, compared to the hyaluronic acid hydrogel and collagen scaffold. | - | Renal ECM was noted as suitable for RPTE cell seeding, maintaining renal cell properties. |
Kim [129] | 2022 | Immersion/ agitation | WTC11 and CMC11 iPSC cell line | - | To determine if it can accurately replicate human kidney development, evaluate the potential role of an acellular kidney (as a hydrogel) in the maturation of hPSC-derived kidney organoids. | The male NOD/SCID mice received renal subcapsular transplantation of kidney organoids that were harvested and combined with 0.1% kidney acellular hydrogel. | Applying the kidney-decellularized ECM (as a hydrogel) enables kidney organoids' extensive vascularization and maturation. |
Hsu [9] | 2022 | Perfusion | Tubular epithelial cells, mouse kidney progenitor cells, endothelial cells. | Artery and Ureter | - | - | Recellularized kidneys produce urine and provide renal function, including reabsorption. |
Geraldine Haeublein [22] | 2022 | Perfusion (1 ml/min) Through Ureter, Artery, and Vein (Protocol 3 was conducted via Artery) | HMEC | Artery | To create a rat-human bio-artificial kidney by formulating a procedure that partially substitutes human endothelial cells in a rat's kidney. | Recellularized kidneys were transplanted in rats, achieving almost complete perfusion at the vascular tree and urine production within 60 minutes. | The first method presented the best decellularization with the most parenchyma disruption and vascular permeability. However, ECM preservation was best achieved in other groups. |
Ghorbani [55] | 2022 | Perfusion (4 ml/ min) | MSCs | - | Evaluation of residual SDS amount in decellularized kidney | - | Methylene blue can be an excellent colorimetric method for evaluating residual SDS on decellularized scaffolds. |
Corridon [105] | 2022 | Perfusion (4 ml/ min) Through Artery | - | - | Evaluation of the feasibility of intravital microscopy in the assessment of decellularized scaffolds. | - | Intravital microscopy was successfully applied for the examination of transplanted decellularized kidneys. |
Bongolan [35] | 2022 | Immersion/ agitation | human adult primary renal epithelial cells (RECs) | - | Evaluation of the feasibility of submicellar SDS application. | - | Submicellar application of SDS has led to the retention of growth factors, proteins, and cytokines, providing great potential for further cell proliferation and uniform cell distribution. |
Zhou [85] | 2021 | Perfusion Heparin was immobilized on scaffolds. | HUVECs | - | Evaluation of the effectiveness of heparinization on neovascularization. | It was effectively implanted and secured by positioning the modified scaffold within the capsular bag that formed between the renal sac and renal parenchyma. | Heparin perfusion resulted in better preservation of morphology along with optimal anticoagulated and biomechanical properties. Moreover, further release of EGF and angiogenesis was improved. |
Zhang [26] | 2021 | Perfusion Through artery | Endothelial progenitor cells (EPCs) | - | Evaluation of the feasibility of decellularized fibrotic kidneys for further bioengineered application. | - | Decellularized fibrotic kidneys could be used as bioengineered organs like normal kidneys. |
Xie [84] | 2021 | Perfusion (1 ml/ min) Through: Artery and Ureter | HUVECs | Artery | Evaluation of anti-inflammatory effects of heparinization on angiogenesis and re-endothelialization. | Subcutaneous implantation of modified and non-modified kidney recellularized slices was performed in nude mice. | Modifying heparin has led to anticoagulative and anti-inflammatory effects inducing angiogenesis and re-endothelialization. |
Taylor [75] | 2021 | Perfusion (80 mmHg) Through Artery | - | - | Assessment of the feasibility of perfusion decellularization of whole body organs. | Perfusion decellularization is a method with good outcomes, providing optimal biomechanical properties while preserving ECM characterization. | |
Sobreiro [119] | 2021 | Immersion/ agitation | human renal progenitor cells hRPCs | - | Evaluation of the feasibility of decellularized articulated porcine kidney ECM for further uses in renal injuries developing into chronic kidney disease. | - | Particles achieved from ground-decellularized kidneys have immense potential as valuable resources in regenerative nephrology. By minimizing the surgery requirement, they can effectively reverse minor injuries at a localized level, ultimately preventing the development of chronic renal dysfunction. |
Shahraki [23] | 2021 | Immersion/ agitation | Human ADMSCs | - | To evaluate an effective method for rat kidney decellularization suitable for the proliferation of human ADMSCs. | - | They found SDS to be a more effective decellularization agent than Triton X-100; recellularized scaffolds experienced re-epithelialization and re-endothelialization, providing a suitable scaffold for the proliferation and differentiation of seeded stem cells. |
Sant [36] | 2021 | Immersion/ agitation | - | - | To evaluate the effect of glycation on the biomechanical specification of the scaffold following the decellularizing process. | - | Matrix crosslinking mediated by advanced glycation has culminated in enhanced biomechanical properties of the decellularized scaffold in a dose-dependent manner. |
Manalastas [39] | 2021 | Perfusion through Artery 1- 15 ml/ min 2- 30 ml/ min 3- 45 ml/ min Along with Sonication: 1- 0 W 2- 60 W 3- 120 W | - | - | Evaluation of the effect of SDS concentration, Perfusion rate, and sonication on time needed for decellularization. | - | All evaluated parameters had a significant effect on acellularization time. Sonicator power had a significant effect on the scaffolds' microstructure integrity, causing minimal integrity alteration. |
Mallis [19] | 2021 | 1- Rotary shaker approach 2- Magnetic stirrer approach | Human Wharton’s Jelly Mesenchymal Stromal Cells | - | Evaluation of two alternative decellularization techniques to establish a more cost-effective decellularizing method. | - | Both approaches were successful in reaching decellularized status. However, Magnetic Stirrer was more successful regarding biochemical and histologic properties, providing good outcomes with decellularization and preservation of kidney composition. |
Ko [41] | 2021 | NM | Human proximal tubular epithelial cell line, HK2, and murine macrophage cell line | - | Evaluation of the effectiveness of bioactive compounds on functionalizing acellular porcine kidney scaffold. | ICR mice randomly received six types of kidneys regarding the bioactive component in the decellularized kidney. | Applying such bioactive components with acellularized kidneys has enhanced cell proliferation and induction of angiogenesis. Moreover, such regenerated kidneys experienced decreased fibrosis and inflammation and increased GFR. Notably, the PDRN/TI-EVs combination demonstrated an enhanced therapeutic effect in facilitating neovascularization, mitigating renal fibrosis, and activating pro-reparative macrophages. |
Kim [10] | 2021 | Perfusion | Stem cells | - | To evaluate the decellularization method with further stem cell transplantation on angiogenesis. | - | Vascularization in regenerated organs can make a potential organ for organ transplantation. |
Keshvari [24] | 2021 | Perfusion (1-2 ml/ min) Through Artery | Human umbilical cord mesenchymal stromal/stem cells (hUC-MSCs) | - | To compare the outcomes following decellularization with sodium lauryl ether sulfate and sodium dodecyl sulfate. | Scaffolds were allotransplanted into back muscle of each rat. | Although both detergents reached complete decellularization, SLES culminated in better preservation of ECM integrity. Moreover, both groups had the same angiogenesis, cell proliferation, and migration. Hence, SLES was introduced as a detergent of choice for kidney decellularization. |
Corridon [38] | 2021 | Perfusion (5 ml/ min) Through Artery | - | - | To analyze how pulsatile blood flow affects decellularized porcine kidneys' vascular architecture and functionality. | Acellular and native kidneys were continuously perfused with whole blood at: 1- normal physiological (650 ml/min) 2- 500 ml/min 3- pathophysiological rate (200 ml/min) | Notably, the glomerular microarchitecture was significantly disrupted by the pulsatile blood perfusion. |
Ullah [45] | 2020 | Immersion/ agitation | Human iPSC-lines | - | Evaluating the role of ECM-related factors (heparan-sulfate proteoglycans) on induction of stem cell differentiation. | - | Seeded cells were specifically differentiated into nephron cells. They concluded that removing heparan-sulfate proteoglycans has prevented further cell differentiation, introducing heparan-sulfate proteoglycans in adult ECM as the main factor inducing further cell differentiation. |
Tajima [56] | 2020 | Freeze-thaw + Perfusion (15 ml/ min) Through Artery | - | - | To evaluate the efficacy of the renal decellularization method in dogs. | - | Decellularization of canine kidneys was successful in preserving renal integrity. |
Sobreiro [40] | 2020 | Immersion/ agitation | human renal progenitor cells (hRPCs) and HUVECs | - | To evaluate whether decellularized ECM of the porcine kidney can substitute tubular basement membrane. | - | Utilizing decellularized matrices in conjunction with primary renal cells has proven invaluable for simulating renal function and disease in a laboratory setting. |
Moradi [54] | 2020 | Perfusion Through Vein | Rabbit adipose-derived mesenchymal stem cell (ASCs) | - | Investigation into the effectiveness of different sterilization methods for decellularized kidney tissue. | - | Among various sterilization methods, PAA 0.5% was introduced as the most effective method, and radiation was shown to be the most disturbing method. |
Hu [16] | 2020 | Perfusion (10 ml/ min) Through Artery | Human ucMSCs | Artery and/ or ureter | Evaluation of efficacy of human umbilical cord mesenchymal stem cell seeding on decellularized kidney. | Patches of recellularized kidneys were transplanted to fibrotic kidneys. | Patches of recellularized kidney was beneficial in restoring kidney function by reducing fibrosis, introducing this technique as an alternative for treating renal fibrosis. |
Feng [18] | 2020 | Perfusion (0.4 mL/min) Through Artery + Freeze-thaw: 1- No freeze-thaw 2- freeze-thaw without Cryoprotectants 3, 4- Freeze-thaw + Cryoprotectants 5- Freeze-thaw + VS83 | - | - | To evaluate and compare the effectiveness of freeze-thaw and cryopreservation mechanisms in preserving vascular integrity within decellularized kidney scaffolds. | - | Freeze-thaw caused severe disruption of vascular integrity, introducing ice-free cryopreservation as a safe technique for further preservation of scaffold vasculature. Moreover, micro-CT imaging might be a valuable tool for evaluating vascular trees. |
Zhang [132] | 2019 | Perfusion (250 µL/ min.) Through Artery | ADSCs and intermediate mesoderm (Induced from ADSCs by adding Wnt agonist) | Artery and Ureter | To evaluate and compare the efficiency of differentiation of ADSCs with ADSCs-induced intermediate mesoderm | - | Intermediate mesoderm cells induced from ADSCs were more well-differentiated to tubular and podocyte-like cells with higher differentiation efficiency than the original stem cells. Consequently, employing scaffolds to induce the differentiation of stem cells may present a practical method for renal regeneration. |
Ullah [44] | 2019 | Immersion/ agitation | HUVEC and human induced pluripotent stem cells (hiPSC) | - | To evaluate the efficiency of VEGF administration on induction of angiogenesis in recellularized kidney. | - | Removing heparin-binding growth factors by eliminating HSPG and HBGF has extensively reduced the ability of stem cells to differentiate. However, using a specific VEGF supplement on a decellularized scaffold culminated in significant differentiation of stem cells to endothelial cells. Hence, they concluded that conditioning scaffold with specific growth factors offers the opportunity to generate functional niches by selectively promoting cell attachment, survival, and differentiation. |
Lih [112] | 2019 | Immersion/ agitation | human renal cortical epithelial cells HRCEpC cells | - | To evaluate the effectiveness of PLGA/ decellularized ECM/Mg(OH)2 advanced mixture scaffold for treating renal diseases. | Male ICR mice's kidneys underwent partial nephrectomy and were treated with PLGA/ECM/Mg(OH)2 scaffolds. | While the inflammatory response to the advanced scaffold was minimal, renal glomeruli were regenerated, and subsequently, renal function was restored after scaffold application compared to the control group. |
Leuning [95] | 2019 | Perfusion Through Vein and Artery | Human glomerular microvascular endothelial cells (hgMVECs) and Human pluripotent stem‐cell‐derived ECs. | Artery, Vein, and Ureter | To evaluate the adequacy of their novel arteriovenous delivery system for further enhancement of recellularization (Re-endothelialization) outcomes. | - | After preloading vascular matrix with VEGF and angiopoietin 1 in decellularized scaffold, by application of a novel arteriovenous delivery system, complete re-endothelialization of the kidney glomeruli and capillaries was achieved with using Human pluripotent stem‐cell‐derived ECs. Moreover, they showed complete ability of the recellularized kidney to be perfused with human whole blood. |
Kajbafzadeh [48] | 2019 | Perfusion (10 ml/ min) Through Artery | - | - | Evaluation and comparison of outcomes following transplantation by two distinct protocols for kidney decellularization. | Two sheep received decellularized kidneys from protocol 1, and two received decellularized kidneys from protocol 2. | Utilization of Triton X-100 prior to SDS culminated in better decellularization outcomes with better preservation of vasculature integrity. Moreover, this protocol (1) yielded better results after kidney transplant. |
Hu [2] | 2019 | 1- Perfusion 2- Perfusion + freeze-thaw | - | - | To evaluate and compare the effectiveness of freeze-thawing administration in the decellularization process. | - | The time of decellularization in the third protocol was less than in others. The amount of remnant growth factors was higher following the third protocol. They concluded that simultaneous administration of perfusion and freeze-thaw is a promising method with acceptable outcomes for decellularization. |
Ciampi [88] | 2019 | Perfusion (0.4 ml/min) Through Artery | Human ipsC derived endothelial cells | Primarily, artery. Latly, both vein and artery | Evaluation of the impact of hipsC-eCs in neovascularization induction in decellularized kidney | - | Endothelial cells continuously cover the inner lineage of the vessels. Moreover, specific re-endothelialization was achieved since the vascular structure of the glomeruli was porous despite normal vascular capillaries of other sites. |
Alnazer [142] | 2019 | - | - | - | Comparison of ultra-sonographic properties between normal and decellularized kidneys | - | Quantitative parameters in ultrasonography are shown to be different in decellularized kidneys, altering both textural and spectral parameters. The mid-band fit means and contrast could mainly discern between fresh and decellularized kidneys. |
Ali [110] | 2019 | Perfusion (0.75 L/h) | Human primary kidney cells | - | To evaluate the effectiveness and outcomes of using kidney-decellularized ECM as a bio-ink for bioprinting. | - | The bioprinted human kidney cells within the bioink displayed a high level of viability and underwent maturation. Additionally, the bioprinted renal constructs successfully emulated the structural and functional characteristics of the native renal tissue. |
Zambon [79] | 2018 | Perfusion Through Artery | MS1 endothelial cells | - | To compare the outcomes (Preservation of vascular integrity) following two distinct decellularizing methods. | - | The second protocol successfully removed cells and preserved vascular integrity. Preserving vascular integrity culminated in patency of vasculatures following blood perfusion in the recellularized scaffold. |
Xue [90] | 2018 | Perfusion Through Artery and Ureter | ADSCs | Artery and Ureter | To evaluate the impact of ADSC seeding on the decellularized kidneys. | - | ADSCs were successfully proliferated, adhered to, and differentiated to endothelial and tubular structures, introducing ASDCs as a source of cells regenerating kidney. |
Wang [83] | 2018 | Perfusion Through Artery | Human umbilical vein endothelial cells (HUVECs) | Artery | To evaluate the impact of heparin on the decellularized kidney on in-vivo outcomes. | - | Heparinized scaffolds experienced less thrombosis formation, providing a good site for reendothelialization and neovascularization. |
Su [113] | 2018 | Immersion/ agitation | immortalized human glomerular endothelial cells | - | Evaluation of the adequacy of decellularized ECM hydrogel for cell culture. | - | Encapsulated or cultured cells on hydrogels were highly survived and proliferated within one week. However, encapsulated cells significantly expressed a lower amount of several genes. |
Padalhin [134] | 2018 | Perfusion (0.5 ml/ min) Through Artery | Calf pulmonary arterial endothelium | 1- Artery 2- Ureter | To establish a model for further in-vitro studies of kidney diseases by using decellularized kidneys. | - | Based on the outcomes, it is possible to attain decellularized kidneys with intact microstructures and renal proteins in a comparatively shorter timeframe (12 hours) than the established protocols (96-120 hours). The simplified design of the kidney bioreactor preserved the sterility of the decellularized kidney without cells and allowed for the convenient maintenance of cell-immobilized constructs for one week. |
Kajbafzadeh [133] | 2018 | NM | - | - | To establish a surgical method for bilateral transplantation of acellularized kidneys. | - | The potential of concomitant bilateral kidney transplantation to serve as a workable and realistic approach in this context is noteworthy, as it may pave the way for subsequent investigations aimed at clinical applications. |
Hussein [34] | 2018 | Perfusion (25 ml/min) | Pig kidney epithelial cell line (PKs) | Artery | To evaluate the bio/ hemo compatibility of decellularized kidneys. | Subcutaneous implantation of native and decellularized cortex and medulla was performed in 24 male mice. | Decellularization was successfully achieved. As the scaffold was exposed to blood, good hemocompatibility was yielded. 97.7% of DNAs were utterly removed. In-vitro studies showed the absence of a human immune response to the scaffold. Moreover, the scaffold was not cytotoxic to the seeded cells. |
Fedecostante [109] | 2018 | Perfusion | Immortalized human renal proximal tubule epithelial cells | - | To establish a model for evaluation of nephrotoxicity of drugs based on recellularized kidneys. | - | In comparison with 2D in vitro cultures, 3D recellularized kidneys showed more sensitivity, providing more information regarding drug nephrotoxicity. |
Bombelli [107] | 2018 | Immersion/ agitation | Nephrosphere (NS) cells are composed of renal stem/progenitorlike cells. Each cell line was received from the same patient. | - | To assess the ability of NS cells to regenerate various segments of the nephron within renal ECM scaffolds derived from decellularized human renal tissue slices. | - | NS cells were differentiated to proximal and distal tubes and endothelial tissue. Hence, they advocated that NS cells might be an acceptable cell, providing differentiation of recellularized scaffolds toward nephron regeneration. |
Almelkar [47] | 2018 | Perfusion Through Artery | - | - | To decellularize a sheep kidney with the perfusion method and evaluate the architecture using the Edge detection method. | - | The edge detection method provided an acceptable 3D view of scaffold vasculature. . |
Uzarski [102] | 2017 | Perfusion Through Artery | Immortalized Madin-Darby Canine Kidney (MDCK) epithelial cells | Artery | To evaluate Resazurin's feasibility for cell culture adequacy detection in recellularized scaffolds. | - | Resazurin is a safe, inexpensive, and non-invasive method for detecting cell populations in recellularized scaffolds, providing a better view of cell viability and proliferation within the scaffold without sacrificing tissue. |
Sambi [98] | 2017 | Perfusion Through Artery | Embryonic Stem Cell Derived Renal Progenitors | Ureter | To evaluate the adequacy of decellularized rat kidney as a model for evaluation of stem cell differentiation. | - | Before being introduced to the acellular organ, it seems crucial for the stem cells to undergo differentiation into kidney progenitor cells to facilitate the regeneration of kidney structures with the assistance of the extracellular matrix. |
Remuzzi [92] | 2017 | Perfusion Through Artery | The R1 mouse pluripotent embryonic stem (mES) | Artery, Ureter, and Vein | To evaluate the efficacy of in vivo recellularization and compare the outcomes with in vitro recellularization. | Decellularized scaffolds were transplanted in an orthotopic pattern. | Implantation of acellular scaffolds in rats does not result in repopulating these scaffolds with host cells. Therefore, it becomes essential to perform in vitro recellularization. However, the process of recellularizing acellular kidney scaffolds in a controlled laboratory environment is hindered by significant physical barriers that must be identified and understood. |
Poornejad [91] | 2017 | Perfusion (gradual increase from 10 to 35 ml/ min) Through Artery | Madin–Darby Canine Kidney (MDCK) epithelial cells. Cells were labeled with iron-oxide for further detection by MRI. | 1- Artery with high pressure 2- Ureter with high pressure 3- Ureter under moderate vacuum pressure | To compare the outcomes following three distinct recellularization methods and evaluate the adequacy of cell labeling using iron oxide and detection by MRI. | - | The distribution of reseeded, iron-oxide-labeled cells was well evaluated by using MRI. The recellularized kidneys exhibited a significantly more homogeneous distribution of cells when a moderate vacuum pressure of 40mmHg was applied to perfuse the cells through the ureter. |
He [21] | 2017 | Perfusion (10 ml/ min) Through Artery | Primary renal cell (PRC) and Mesenchymal stromal cell (MSC) | Artery | Optimization of SDS concentration and duration of perfusion for rat kidney decellularization to achieve best ECM characteristics. | - | The level of sGAG was significantly higher in 4 h approaches. No significant difference is found between approaches regarding remnant DNA. Many growth factors are preserved in 4 h approaches, especially with decreasing SDS concentration. However, a further decrease in SDS concentrations than 0.125% yielded no significant changes in the amounts of growth factors. |
Fischer [37] | 2017 | Immersion/ agitation (shaker at 50 rpm) | Human iPSC-derived intermediate mesoderm (IM) cells | - | To assess and contrast the effectiveness of decellularization, structure preservation, composition, cell attachment, and viability among three different detergents, namely Triton X-100, SDS, and SDC, employed at various temperatures. | - | ECM integrity was mainly associated with ambient temperature. However, preserving GAG, cytokines, and collagens was strongly associated with the detergent, especially optimal outcomes at 4°C by SDS 1%. The viability of reseeded cells was best achieved by SDC, being highly related to the preservation of cytokines. Hence, the decellularization process using a 1% SDS solution at 4 °C yielded the most favorable results regarding structural and composition scores. In contrast, using a 1% SDC solution at the same temperature resulted in lower structural and composition scores but showed a significantly improved cell performance score. |
Chani [72] | 2017 | Perfusion (18 ml/ min) Through Artery | Undifferentiated murine C3H10T½ cells. | Artery | To assess the impact of cryopreservation on outcomes following the decellularization process. | - | The ECM framework remains intact after kidney cryopreservation, demonstrating its robustness. The structural integrity of these frameworks was further enhanced, ensuring their durability. The decellularized structures were efficiently repopulated by scaffolds, regardless of the condition of the kidneys, indicating their equal potential for recellularization. |
Wang [121] | 2016 | Perfusion (8 ml/min) Through Artery | endothelial progenitor cells (EPCs) | Vein | To evaluate the role of seeded EPCs on decellularized scaffolds. | - | The administration of exogenous EPCs creates a favorable microenvironment within decellularized renal scaffolds, facilitating the process of angiogenesis and vasculogenesis and ultimately aiding in the recovery of the kidney following renal injury. |
Poornejad [33] | 2016 | Immersion/ agitation (70–80 r/min) 1- Approaches 1, 2, and 4 were on shaker at room temperature. 2- Approach 3 was on a shaker incubator at 37 °C. | Human renal cortical tubular epithelium (RCTE) cells Cells were labeled with lipophilic tracer DiI A Resazurin reduction assay was conducted to evaluate cell viability, proliferation, and distribution. | - | To compare the effectiveness of various decellularizing agents on acellular renal tissue. | - | Protease enzymes achieved minimal efficacy in cell removal and maximal destructive effects on collagenous structure. NaOH was the fastest in decellularizing with optimal ECM interactions; however, it resulted in maximal disturbance of ECM and collagen integrity. Detergents had less altered ECM integrity; however, they were less beneficial than NaOH in cell removal. |
Poornejad [80] | 2016 | Perfusion (10 ml/ min, increased 2 ml/ min q15 min in constant pressure) Through Artery | Human RCTE cells | - | To compare the outcomes following four distinct sterilization methods after decellularization. | - | Gamma irradiation was the most destructive method, decreasing further cell adhesion, proliferation, and mechanical properties. Besides, peracetic acid 0.2% in 1M NaCl was the best sterilizer with acceptable outcomes preserving renal ECM integrity with optimal ECM interactions. |
Poornejad [32] | 2016 | Perfusion (10 ml/ min with an increase of 1.5 ml/ min each 30 min to reach 40-50 ml/min) Through Artery | Human renal cortical tubular epithelium (RCTE) cells | - | To evaluate the effectiveness of adding osmotic shock to previous conventional decellularizing methods. | - | The main advantage of using osmotic shock in decellularization is reducing the time exposure to SDS, providing better cell removal and ECM integrity preservation. Moreover, scaffolds decellularized with osmotic shock showed faster cell proliferation with better preserved GAG and ECM interactions. |
Nagao [115] | 2016 | Immersion/ agitation | Primary HKMECs and HUVECs | - | To evaluate the adequacy of decellularized human kidney hydrogel in promoting endothelial cell proliferation. | - | HKMECs cultured on hydrogel displayed a distinct gene expression pattern compared to those cultured on Collagen-I. Specifically, the expression of genes indicative of cellular quiescence and maturation was upregulated, while genes associated with proteolytic activity and cell surface activation showed a decrease in expression. This suggests that the hydrogel culture environment promotes a state of cellular quiescence and maturation while inhibiting proteolytic activity and cell surface activation. |
Mei [114] | 2016 | Perfusion (8 ml/ min) Through Artery | Human umbilical vein endothelial cells (HUVEC) | - | To evaluate the adequacy of recellularization with HUVEC on acellular kidney neovascularization. | Transplantation of kidneys was conducted. | The acellular kidney promoted HUVEC proliferation, adhesion, and significant induction of angiogenesis with increased amounts of VEGF. |
Lih [111] | 2016 | Immersion/ agitation | Human renal cortical epithelial (HRCE) cells, renal epithelial cell basal medium, and renal epithelial cell. | - | To evaluate the adequacy of mixed decellularized-PLGA scaffold in restoring kidney function after partial nephrectomy. | - | The proliferation of cells was increased as the concentration of ECM increased. Utilizing a PLGA scaffold that incorporates 10% of ECM has demonstrated its efficacy as a matrix for the restoration and reconstruction of glomerulus and blood vessels.. |
Du [96] | 2016 | Perfusion Through Artery | Induced pluripotent stem cells (iPSCs) differentiated to renal progenitor and endothelial cells. | Artery | Evaluation of the adequacy of employing human iPSCs renal progenitor cells and endothelial cells in decellularized kidney to regenerate kidney function. | Regenerated kidneys were implanted subcutaneously | Regenerated kidneys were implanted subcutaneously. A functional whole kidney could be generated by utilizing clinically relevant, expandable patient-specific renal progenitors and endothelial cells to repopulate decellularized native kidneys. This approach holds promise for restoring kidney function and could offer a viable solution for patients needing renal replacement therapy. By using patient-specific cells, the risk of rejection or immune response could be minimized, increasing the likelihood of successful transplantation and long-term functionality of the regenerated kidney. |
Abolbashari [103] | 2016 | Perfusion | Porcine renal cells | Artery | Evaluation of renal function following recellularization by assessment of sodium uptake, EPO production, and hydrolase activity. | - | Sodium uptake, hydrolase activity, and EPO production were also evaluated—the majority of distributed cells developed into proximal tubular cells and tubular-like cells. Seeded cells were shown to provide the aforementioned renal functions. |
Zhang [120] | 2015 | Perfusion (8 ml/ min) Through Artery | Endothelial progenitor cells (EPCs) | - | To explore regenerating renal vessels following the transplantation of whole decellularized kidneys in an in vivo setting. | Recellularized kidneys transplanted orthotopically to the group underwent nephrectomy. | Spontaneous recanalization, new veins, and arteries regenerated. |
Wang [31] | 2015 | Perfusion (15 ml/ min) Through Artery | - | - | To compare the outcomes following various decellularizing agents. | - | ECM integrity preservation, cell removal, and xenoantigens removal were best achieved following SDS 1%. |
Uzarski [100] | 2015 | Perfusion Through Artery | Renal Cortical Tubular Epithelial Cells | Artery | To evaluate the outcomes following RCTE cell seeding and Resazurin assessment for cell viability and proliferation in the recellularized kidney. | - | Resazurin Perfusion Assay is used to evaluate cell proliferation and viability. The tubular ECM niche in the renal cortex was predominantly occupied by RCTE cells, which undergo proliferation and organize themselves into tubular structures during a seven-day perfusion culture period. |
Uzarski [101] | 2015 | Perfusion Through Artery | immortalized Madin-Darby canine kidney (MDCK) cells or primary human renal papillae-derived CD133/1+ Cells. | Artery or Ureter | To evaluate the feasibility of a dual-purpose bioreactor to monitor the adequacy of recellularization. | - | This study's enhanced kidney bioreactor design surpasses previous models by integrating ureteral and arterial pathways for recellularization. Arterial (high-pressure) recellularization showed better results compared to others. Resistance to fluid flow through the scaffold, referred to as ΔP, declines as cell loss occurs during the decellularization process. Conversely, it rises to almost normal levels for intact organs upon the recellularization of the kidney. |
Rafighdoust [82] | 2015 | Immersion/ agitation | Human adipose‐derived mesenchymal stem cells: 1- No cell + no Chondroitin sulfate 2- Cell + no Chondroitin sulfate 3- Cell + Chondroitin sulfate | - | To evaluate the impact of chondroitin sulfate on physical and biochemical properties of recellularized kidney scaffolds. | - | Chondroitin sulfate-induced cell proliferation, adhesion, and migration. |
Poornejad [71] | 2015 | 1- Freeze-thaw + Perfusion 2- Perfusion Through Artery Perfusion is conducted with gradual increase in flow rates | Human RCTEs | - | To assess the impact of freezing and thawing on the native and decellularized extracellular matrix | - | Although freeze-thawing was shown to have destructive effects on native kidneys, adverse effects were found much less on decellularized kidneys in the absence of cryoprotectants. |
Peloso [7] | 2015 | Perfusion (12 ml/ min) Through Artery and Ureter | - | - | To evaluate the adequacy of decellularized human discarded kidneys regarding the preservation of their vasculature and growth factors for further in vivo application. | - | The well-preserved structure and functional vasculature of discarded human kidneys make them ideal for renal scaffolds. Moreover, owing to their angiogenic properties, these kidneys contain growth factors (GFs) that are essential for achieving a satisfactory recellularization of the scaffold in vivo. |
Peloso [78] | 2015 | Perfusion (70 ml/ h) Through Vein | Human pancreatic carcinoma cells (MIA PaCa-2) | Artery | Development and optimization of decellularizing protocol for rat kidneys. | Orthotopic transplantation of recellularized kidneys was performed. | Utilization of simultaneous two detergents resulted in successful cell removal with ECM integrity preservation. |
Ofenbauer [99] | 2015 | Immersion/ agitation | Murine embryonic stem cells (mESCs) | - | To evaluate the effectiveness of the simultaneous use of paraffin slices and 2D cell culture to compare the outcomes following various decellularization methods. | - | The influence of previously paraffin-embedded decellularized ECMs on stem cell differentiation has been successfully demonstrated. This method presents a promising avenue for determining the most effective decellularization protocols for repopulating 3D tissue scaffolds with embryonic stem cells and other tissue-specific cell types. |
Liu [74] | 2015 | Perfusion (2 ml/ min) Through Artery | - | - | To develop a complete kidney acellular scaffold through peristaltic pump perfusion and to investigate the scaffold's ability to preserve extracellular proteins. | - | The micro-peristaltic pump successfully removed cells from rat kidneys, providing a suitable environment for further cell seeding. |
Guan [27] | 2015 | Perfusion (2 ml/ min) Through Artery | Mouse embryonic stem (ES) cells | Artery and Ureter | Development of a more efficient and accelerated method for decellularizing and recellularizing kidney scaffolds. | Transplantation of acellular and recellularized kidneys was performed in an orthotopic pattern. | Recellularized scaffolds were easily reperfused with blood, producing urine without any leakage. Proliferated seeded cells were distributed within tubules, vasculatures, and glomeruli. |
Guan [30] | 2015 | Perfusion (10 ml/ min) Through Artery | Mouse embryonic stem cells (mESCs) | Multiple puncture | To develop and evaluate decellularized scaffolds from porcine kidneys as a source of kidney for further kidney regeneration. | - | Decellularization was conducted successfully with optimal biological, vascular, and ECM integrity preservation. Moreover, the growth factors in acellular scaffolds remained the same as in native kidneys. |
Choi [77] | 2015 | Immersion/ agitation (200 rpm) | - | - | Development of porcine acellular kidney scaffold and comparing the outcomes and efficacy of two distinct decellularizing agents. | - | Triton X-100 was the optimal detergent for kidney decellularization, providing better biomechanical and biochemical properties and optimized biocompatibility. Moreover, Triton X-100 could preserve higher growth factors with less structural disturbance. |
Caralt [25] | 2015 | Perfusion Through Artery | Purified human endothelial cells derived from iPSCs and Immortalized human renal cortical tubular epithelial (RCTE) cells | Artery | Comparing and evaluating outcomes after utilization of three distinct decellularizing protocols. | Transplantation of acellular and recellularized kidneys was conducted. | The second protocol successfully yielded optimal outcomes with kidney decellularization. Further transplantation of recellularized kidneys of the second protocol was successfully re-perfused with blood, providing a suitable environment for further cell proliferation. |
Batchelder [53] | 2015 | Perfusion Through Artery | Human embryonic stem cells (hESC) were directed toward differentiation to renal lineage by the application of supplements | Artery or Ureter | Evaluation of adequacy of decellularized monkey kidneys in induction of renal differentiation of hESCs. | - | The expression of renal lineage markers increased in hESC when cultured in decellularized scaffolds without cytokine or growth factor stimulation. This indicates that the ECM plays a crucial role in guiding the differentiation of renal lineage. These findings further suggest that natural scaffolds have a more remarkable ability to enhance the expression of renal lineage markers compared to embryoid body cultures |
Yu [135] | 2014 | Perfusion (8 ml/min) | - | - | To evaluate the outcomes and ability of renal function restoration following application of decellularized kidneys' graft to rats underwent partial nephrectomy. | Transplantation of the decellularized kidneys was performed. The left kidney of each rat underwent a surgical procedure where approximately one-third of its tissue was excised transversely. Following this excision, scaffolds of similar size were grafted onto the cut-end by suturing them to the external capsules. In the control group, the cut end was directly sutured without grafting. | The study detected an increase in the size of the kidneys, accompanied by the presence of regenerated renal parenchyma cells within the repaired area containing the grafted scaffold. Furthermore, there was a notable rise in the number of nestin-positive renal progenitor cells in the kidneys that underwent scaffold grafting compared to the control group. Moreover, the analysis of radionuclide scans exhibited a significant recovery of renal functions at the six-week post-implantation stage. |
Vishwakarma [46] | 2014 | Perfusion Through Artery | - | - | To evaluate the feasibility of goat kidney decellularization. | - | - |
Ko [81] | 2014 | Perfusion | Vascular endothelial cells expressing GFP protein (MS1) | Artery and Vein | To evaluate the impact of antibody conjugation of vasculatures on outcomes after recellularized kidney implantation. | Implantation was performed: 1- Recellularization without antibody conjugation 2- Recellularization with CD31 antibody conjugation. | The conjugation of CD31 antibodies to the vascular matrix markedly improved the retention of endothelial cells on the vasculatures. This enhanced retention subsequently contributed to an improved vascular patency of the implanted scaffold. The outcomes of this study provide compelling evidence supporting the effectiveness of our endothelial cell seeding method when combined with antibody conjugation, as it effectively enhances both endothelial cell attachment and retention, ultimately leading to the achievement of vascular patency in an in vivo tissue-engineered whole kidney model. |
Finesilver [97] | 2014 | Immersion/ agitation | HK-2 and HES | - | To evaluate the effectiveness of kidney-derived serum-free conditioned media on induction of differentiation of human embryonic stem cells seeded on decellularized kidneys. | - | The growth and expansion of HES are influenced by the intricate structure provided by the scaffold. NPHS-1, REN, AQP-1, SLC2A2, and ANPEP expression levels were higher when the HES were cultivated on a scaffold than when grown on collagen. Similarly, the levels of these genes were also higher when the HES were grown on a scaffold compared to when they were grown on Matrigel. Moreover, it has been observed that culturing HES in 5% kidney-derived serum-free conditioned media can result in the upregulation of NPHS-1, REN, and EPO. |
Chae [29] | 2014 | Immersion/ agitation | Primary human kidney cells | - | To develop an acellular kidney scaffold and evaluate its physical and biochemical properties. | Two types of scaffolds were transplanted in mice. | The ability of the Triton X-100 treated scaffold for water uptake was higher with increased porosity, providing better preservation of ECM proteins and growth factors and excellent biocompatibility. The biomechanical properties of SDS-treated scaffolds were optimal. |
Bonandrini [76] | 2014 | Perfusion (0.4 ml/ min) Through Artery | The R1 pluripotent mES cells | Artery | To evaluate the effectiveness of decellularizing protocol for rat kidneys. | - | A decellularized kidney was achieved with successful cell removal, preservation of ECM proteins, vasculature integrity, and 3D architecture. Moreover, recellularization was uniformly performed with meso-endo-dermal differentiation. |
Song [89] | 2013 | Perfusion (1.5 ml/min) Through Artery | Human umbilical vein endothelial cells (HUVEC) | - | To evaluate in vitro and in vivo function of recellularized kidneys in rats. | Transplantation of recellularized kidneys was performed in an orthotopic pattern. | Perfusion of the resulting grafts through their intrinsic vascular bed in vitro produced rudimentary urine. Subsequently, upon transplantation in the orthotopic position in rats, the grafts were perfused by the recipient's circulation, enabling urine production through the ureteral conduit in vivo. |
Orlando [42] | 2013 | Perfusion (12 ml/ min) Through Artery and Ureter | - | - | To develop a human kidney acellular scaffold and evaluate the scaffolds' biochemical, ECM properties, and vascular integrity. | - | The decellularization protocol utilizing SDS effectively eliminated the cellular component within the kidneys while preserving the structural and biochemical characteristics of the ECM. When tested in a chick chorioallantoic membrane assay, samples of human renal ECM scaffolds demonstrated the ability to promote angiogenesis. Notably, the inherent vascular network within the human renal ECM scaffolds maintained its flexibility. |
O’Neill [94] | 2013 | Immersion/agitation | Mouse kidney stem cells (KSCs) and Mouse mesenchymal stem cells (MSCs) | - | To develop a decellularized kidney scaffold and to evaluate the feasibility of producing hydrogels, sheets, and solutions from scaffolds. To compare the functions of the stem cells reseeded on scaffold regarding its origin. | - | Kidney stem cell function regulation is influenced by all three forms of the ECM, each exerting unique structural and compositional effects. Notably, when kidney stem cells were cultured on papilla ECM, they consistently exhibited reduced proliferation, heightened metabolic activity, and distinct differences in cell morphology, alignment, and structure formation compared to those cultured on cortex and medulla ECM. Interestingly, these effects were not observed in mesenchymal stem cell cultures corresponding to the kidney. These findings suggest that the ECM derived from specific tissues and regions can serve as an effective substrate for investigating therapeutic stem cells in laboratory settings. |
Nakayama [52] | 2013 | Immersion/ agitation | Human embryonic stem cells (hESCs) | - | To evaluate the outcomes and factors affecting differentiation following recellularizing the acellular kidney with hESCs. | - | Proteomic analysis showed the preservation of growth factors, antimicrobial proteins, stress proteins, and complement components within the scaffold. Kidney-associated genes had increased expression after recellularization. Decellularized scaffolds possess an inherent spatial capacity to impact the differentiation of human embryonic stem cells (hESC) by physically molding cells into structures and phenotypes suitable for tissue development. |
Sullivan [73] | 2012 | High-throughput decellularization system | Primary human renal cells | - | To evaluate the feasibility and effectiveness of the novel method of high-throughput decellularization system in kidney regeneration. | - | This method ensures the clearance of porcine cellular material while preserving the extracellular matrix and cellular compatibility of these renal scaffolds. |
Ross [93] | 2012 | Perfusion Through Artery and Ureter | Murine ESCs | Artery | Evaluation of signals' presence within decellularized scaffolds induces further differentiation after recellularization. | - | Evidence revealed a signaling process between the matrix and cells within acellular whole organ scaffolds. This signaling pathway guides pluripotent precursor cells toward differentiation into the endothelial lineage. Furthermore, producing a mouse basement membrane facilitates the remodeling of scaffolds derived from host (rat) cells, thereby warranting further investigation as a promising avenue for xenotransplantation. |
Park [143] | 2012 | Perfusion (50 ml/ min) | - | - | To develop whole organ decellularizing method. | - | - |
Orlando [28] | 2012 | Perfusion (12 ml/ min) Through Artery | Immortalized Murine hematopoietic support (MS1) endothelial cell line | - | To develop porcine acellular kidney scaffold and to evaluate the outcomes after implantation. | Transplantation of kidneys was performed. | Notably, no instances of blood extravasation were observed. Examination of the explanted scaffolds revealed well-preserved renal ultrastructure. Inflammatory cells in the pericapsular region and complete thrombosis of the vascular tree were also evident, indicating an immune response and blood clotting, respectively. |
Nakayama [51] | 2011 | Immersion/ agitation | Explants from different age groups (fetal, juvenile, adult) and fetal renal cell fractions. | - | To repopulate kidney sections that have been decellularized in a laboratory setting and assess donor age's influence on the recellularization outcomes. | - | Decellularized kidney sections from various age groups can be repopulated with donor cells. Moreover, the donor's age plays a crucial role in determining the efficiency of repopulation. The repopulation of cells was most pronounced when utilizing scaffolds derived from the youngest donors. |
Nakayama [50] | 2010 | Immersion/ agitation | The process of layering fetal kidney explants onto decellularized kidney scaffolds of the same age is being conducted. | - | The fabrication of a decellularized kidney scaffold for further use in the laboratory setting. | - | The significance of age plays a crucial role in the decellularization and recellularization processes. This factor forms the foundation for developing methodologies potentially essential for future in vivo transplantation procedures, catering to patients across various age groups. |
Ross [13] | 2009 | Perfusion Through Artery | Murine pluripotent ES | Artery or Ureter | Decellularizing intact organs in such a way that the matrix signal required to differentiate pluripotent cells is retained. | - | The cells underwent differentiation. Furthermore, cells not in direct contact with the basement membrane matrix underwent apoptosis, forming lumens. These findings strongly imply that the ECM plays a crucial role in guiding the regenerative process of the kidney. |
Liu [14] | 2009 | Perfusion Through Artery | - | - | Evaluating the feasibility of perfusion for kidney decellularization. | - | - |