The increase in the incidence of chronic kidney diseases that progress to end-stage renal disease has become a significant health problem worldwide. While dialysis can maintain and prolong survival, the only definitive treatment that can restore renal function is transplantation. Unfortunately, many of these patients die waiting for transplantable kidneys due to the severe shortage of donor organs. Tissue engineering and regenerative medicine approaches have been applied in recent years to develop viable therapies that could provide solutions to these patients. Cell-based and cell-free approaches have been proposed to address the challenges associated with chronic kidney diseases. Strategies and progress toward developing alternative therapeutic options will be reviewed.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Levin A, Tonelli M, Bonventre J, Coresh J, Donner JA, Fogo AB et al (2017) Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet (London, England). 390(10105):1888–1917
Hart A, Smith JM, Skeans MA, Gustafson SK, Wilk AR, Robinson A et al (2018) OPTN/SRTR 2016 annual data report: kidney. Am J Transpl 18:18–113
Saran R, Robinson B, Abbott KC, Agodoa LYC, Bhave N, Bragg-Gresham J et al (2018) US renal data system 2017 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis 71(3:Suppl1):A7
Schena FP (1998) Role of growth factors in acute renal failure. Kidney Int Suppl 66:S11–S15
Carley WW, Milici AJ, Madri JA (1988) Extracellular matrix specificity for the differentiation of capillary endothelial cells. Exp Cell Res 178(2):426–434
Harris RC (1997) Growth factors and cytokines in acute renal failure. Adv Ren Replace Ther 4(2 Suppl 1):43–53
Bussolati B, Camussi G (2015) Therapeutic use of human renal progenitor cells for kidney regeneration. Nat Rev Nephrol 11:695
Aggarwal S, Grange C, Iampietro C, Camussi G, Bussolati B (2016) Human CD133(+) renal progenitor cells induce erythropoietin production and limit fibrosis after acute tubular injury. Sci Rep 6:37270
Qi W, Johnson DW, Vesey DA, Pollock CA, Chen X (2007) Isolation, propagation and characterization of primary tubule cell culture from human kidney. Nephrology (Carlton, Vic). 12(2):155–159
Lazzeri E, Crescioli C, Ronconi E, Mazzinghi B, Sagrinati C, Netti GS et al (2007) Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J Am Soc Nephrol 18(12):3128–3138
Kim K, Lee KM, Han DJ, Yu E, Cho YM (2008) Adult stem cell-like tubular cells reside in the corticomedullary junction of the kidney. Int J Clin Exp Pathol 1(3):232–241
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676
Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C et al (2015) Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526(7574):564–568
Martin GR (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA 78(12):7634–7638
Roufosse C, Cook HT (2008) Stem cells and renal regeneration. Nephron Exp Nephrol 109(2):e39–e45
Huls M, Russel FG, Masereeuw R (2008) Insights into the role of bone marrow-derived stem cells in renal repair. Kidney Blood Press Res 31(2):104–110
Lin F, Moran A, Igarashi P (2005) Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in postischemic kidney. J Clin Invest 115(7):1756–1764
Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99(10):3838–3843
Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR et al (2003) Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 10(2):228–241
Shukla D, Box GN, Edwards RA, Tyson DR (2008) Bone marrow stem cells for urologic tissue engineering. World J Urol 26(4):341–349
Humphreys BD, Bonventre JV (2008) Mesenchymal stem cells in acute kidney injury. Annu Rev Med 59(1):311–325
Park DH, Eve DJ (2009) Regenerative medicine: advances in new methods and technologies. Med Sci Monit 15(11):RA233–RA251
Cen L, Liu W, Cui L, Zhang W, Cao Y (2008) Collagen tissue engineering: development of novel biomaterials and applications. Pediatr Res 63(5):492–496
Bryksin AV, Brown AC, Baksh MM, Finn MG, Barker TH (2014) Learning from nature—novel synthetic biology approaches for biomaterial design. Acta Biomater 10(4):1761–1769
Dan P, Velot E, Francius G, Menu P, Decot V (2017) Human-derived extracellular matrix from Wharton’s jelly: an untapped substrate to build up a standardized and homogeneous coating for vascular engineering. Acta Biomater 48:227–237
Borges FT, Schor N (2018) Regenerative medicine in kidney disease: where we stand and where to go. Pediatr Nephrol 33(9):1457–1465
O’Neill JD, Freytes DO, Anandappa AJ, Oliver JA, Vunjak-Novakovic GV (2013) The regulation of growth and metabolism of kidney stem cells with regional specificity using extracellular matrix derived from kidney. Biomaterials 34(38):9830–9841
Ross EA, Williams MJ, Hamazaki T, Terada N, Clapp WL, Adin C et al (2009) Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. J Am Soc Nephrol 20(11):2338–2347
Ross EA, Abrahamson DR, St John P, Clapp WL, Williams MJ, Terada N et al (2012) Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes. Organogenesis 8(2):49–55
Nakayama KH, Batchelder CA, Lee CI, Tarantal AF (2010) Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. Tissue Eng Part A 16(7):2207–2216
Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC (2013) Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med 19(5):646–651
Orlando G, Farney AC, Iskandar SS, Mirmalek-Sani SH, Sullivan DC, Moran E et al (2012) Production and implantation of renal extracellular matrix scaffolds from porcine kidneys as a platform for renal bioengineering investigations. Ann Surg 256(2):363–370
Orlando G, Booth C, Wang Z, Totonelli G, Ross CL, Moran E et al (2013) Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies. Biomaterials 34(24):5915–5925
Peloso A, Petrosyan A, Da Sacco S, Booth C, Zambon JP, O’brien T et al (2015) Renal extracellular matrix scaffolds from discarded kidneys maintain glomerular morphometry and vascular resilience and retains critical growth factors. Transplantation 99(9):1807–1816
Caralt M, Uzarski JS, Iacob S, Obergfell KP, Berg N, Bijonowski BM et al (2015) Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation. Am J Transpl 15(1):64–75
Figliuzzi M, Bonandrini B, Remuzzi A (2017) Decellularized kidney matrix as functional material for whole organ tissue engineering. J Appl Biomater Funct Mater 15(4):e326–e333
Bissell MJ, Aggeler J (1987) Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression? Prog Clin Biol Res 249:251–262
Bonandrini B, Figliuzzi M, Papadimou E, Morigi M, Perico N, Casiraghi F et al (2014) Recellularization of well-preserved acellular kidney scaffold using embryonic stem cells. Tissue Eng Part A 20(9–10):1486–1498
Remuzzi A, Figliuzzi M, Bonandrini B, Silvani S, Azzollini N, Nossa R et al (2017) Experimental evaluation of kidney regeneration by organ scaffold recellularization. Sci Rep 7:43502
Poornejad N, Buckmiller E, Schaumann L, Wang H, Wisco J, Roeder B et al (2017) Re-epithelialization of whole porcine kidneys with renal epithelial cells. J Tissue Eng 8:2041731417718809
Swaminathan M, Stafford-Smith M, Chertow GM, Warnock DG, Paragamian V, Brenner RM et al (2018) Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol 29(1):260–267
Miller BLK, Garg P, Bronstein B, LaPointe E, Lin H, Charytan DM et al (2018) Extracorporeal stromal cell therapy for subjects with dialysis-dependent acute kidney injury. Kidney Int Rep 3(5):1119–1127
Miya M, Maeshima A, Mishima K, Sakurai N, Ikeuchi H, Kuroiwa T et al (2011) Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury. Am J Physiol Renal Physiol 301(2):F387–F395
Chen FM, Zhang M, Wu ZF (2010) Toward delivery of multiple growth factors in tissue engineering. Biomaterials 31(24):6279–6308
Ko IK, Ju YM, Chen T, Atala A, Yoo JJ, Lee SJ (2012) Combined systemic and local delivery of stem cell inducing/recruiting factors for in situ tissue regeneration. FASEB J 26(1):158–168
Elia R, Fuegy PW, VanDelden A, Firpo MA, Prestwich GD, Peattie RA (2010) Stimulation of in vivo angiogenesis by in situ crosslinked, dual growth factor-loaded, glycosaminoglycan hydrogels. Biomaterials 31(17):4630–4638
Reis LA, Borges FT, Simoes MJ, Borges AA, Sinigaglia-Coimbra R, Schor N (2012) Bone marrow-derived mesenchymal stem cells repaired but did not prevent gentamicin-induced acute kidney injury through paracrine effects in rats. PLoS One 7(9):e44092
Bruno S, Grange C, Collino F, Deregibus MC, Cantaluppi V, Biancone L et al (2012) Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One 7(3):e33115
Conflicts of interest
The author declares that they have no competing interests.
Research involving human participants and/or animals
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Yang, H., Atala, A. & Yoo, J.J. Kidney regeneration approaches for translation. World J Urol 38, 2075–2079 (2020). https://doi.org/10.1007/s00345-019-02999-x
- Chronic kidney disease
- Regenerative medicine
- Cell therapy