Abstract
A rising number of patients with acute and chronic renal failure worldwide have created urgency for clinicians and investigators to search out alternative therapies other than chronic renal dialysis and/or organ transplantation. This review focuses on the recent achievements in this area, and discusses the various approaches in the development of bioengineering of renal tissue including recent discoveries in the field of regenerative medicine research and stem cells. A variety of stem cells, ranging from embryonic, bone marrow, endogenous, and amniotic fluid, have been investigated and may prove useful as novel alternatives for organ regeneration both in vitro and in vivo. Tissue engineering, developmental biology, and therapeutic cloning techniques have significantly contributed to our understanding of some of the molecular mechanisms involved in renal regeneration and have demonstrated that renal tissue can be generated de novo with similar physiologic functions as native tissue. Ultimately all of these emerging technologies may provide viable therapeutic options for regenerative medicine applications focused on the bioengineering of renal tissue for the future.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AFS:
-
amniotic fluid stem cells
- EB:
-
embryoid body
- ESC:
-
embryonic stem cells
- ESRD:
-
end stage renal disease
- MSC, MM:
-
metanephric mesenchyme
- UB:
-
ureteric bud
References
Ozaki Y, Nishimura M, Sekiya K, Suehiro F, Kanawa M, Nikawa H, Hamada T, Kato Y 2007 Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev 16: 119–129
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM 1998 Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147
Starly B, Choubey A 2008 Enabling sensor technologies for the quantitative evaluation of engineered tissue. Ann Biomed Eng 36: 30–40
Lin F Renal repair: role of bone marrow stem cells. Pediatr Nephrol (in press)
Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A 2000 Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18: 399–404
Kramer J, Steinhoff J, Klinger M, Fricke L, Rohwedel J 2006 Cells differentiated from mouse embryonic stem cells via embryoid bodies express renal marker molecules. Differentiation 74: 91–104
Odorico JS, Kaufman DS, Thomson JA 2001 Multilineage differentiation from human embryonic stem cell lines. Stem Cells 19: 193–204
Al-Awqati Q, Oliver JA 2006 The kidney papilla is a stem cells niche. Stem Cell Rev 2: 181–184
Barile L, Messina E, Giacomello A, Marban E 2007 Endogenous cardiac stem cells. Prog Cardiovasc Dis 50: 31–48
Dorrell C, Grompe M 2005 Liver repair by intra- and extrahepatic progenitors. Stem Cell Rev 1: 61–64
Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, Crowley D, Bronson RT, Jacks T 2005 Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121: 823–835
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM 2002 Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41–49
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH 2002 Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279–4295
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR 1999 Multilineage potential of adult human mesenchymal stem cells. Science 284: 143–147
Krause D, Cantley LG 2005 Bone marrow plasticity revisited: protection or differentiation in the kidney tubule?. J Clin Invest 115: 1705–1708
Herzog EL, Chai L, Krause DS 2003 Plasticity of marrow-derived stem cells. Blood 102: 3483–3493
Poulsom R, Forbes SJ, Hodivala-Dilke K, Ryan E, Wyles S, Navaratnarasah S, Jeffery R, Hunt T, Alison M, Cook T, Pusey C, Wright NA 2001 Bone marrow contributes to renal parenchymal turnover and regeneration. J Pathol 195: 229–235
Gupta S, Verfaillie C, Chmielewski D, Kim Y, Rosenberg ME 2002 A role for extrarenal cells in the regeneration following acute renal failure. Kidney Int 62: 1285–1290
Morigi M, Benigni A, Remuzzi G, Imberti B 2006 The regenerative potential of stem cells in acute renal failure. Cell Transplant 15: S111–S117
Morigi M, Imberti B, Zoja C, Corna D, Tomasoni S, Abbate M, Rottoli D, Angioletti S, Benigni A, Perico N, Alison M, Remuzzi G 2004 Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J Am Soc Nephrol 15: 1794–1804
Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G 2004 Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury. Int J Mol Med 14: 1035–1041
Yokoo T, Fukui A, Ohashi T, Miyazaki Y, Utsunomiya Y, Kawamura T, Hosoya T, Okabe M, Kobayashi E 2006 Xenobiotic kidney organogenesis from human mesenchymal stem cells using a growing rodent embryo. J Am Soc Nephrol 17: 1026–1034
Duffield JS, Bonventre JV 2005 Kidney tubular epithelium is restored without replacement with bone marrow-derived cells during repair after ischemic injury. Kidney Int 68: 1956–1961
Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, Bonventre JV 2005 Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 115: 1743–1755
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: 1756–1764
Humphreys BD, Bonventre JV 2008 Mesenchymal stem cells in acute kidney injury. Annu Rev Med 59: 311–325
Bonventre JV 2003 Molecular response to cytotoxic injury: role of inflammation, MAP kinases, and endoplasmic reticulum stress response. Semin Nephrol 23: 439–448
Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C 2005 Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol 289: F31–F42
Stagg J, Galipeau J 2007 Immune plasticity of bone marrow-derived mesenchymal stromal cells. Handb Exp Pharmacol 180: 45–66
De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A 2007 Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25: 100–106
Perin L, Giuliani S, Jin D, Sedrakyan S, Carraro G, Habibian R, Warburton D, Atala A, De Filippo RE 2007 Renal differentiation of amniotic fluid stem cells. Cell Prolif 40: 936–948
Bonventre JV 2007 Pathophysiology of acute kidney injury: roles of potential inhibitors of inflammation. Contrib Nephrol 156: 39–46
Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH 1997 Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810–813
Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de Leon FA, Robl JM 1998 Cloned transgenic calves produced from nonquiescent fetal fibroblasts. Science 280: 1256–1258
Baguisi A, Behboodi E, Melican DT, Pollock JS, Destrempes MM, Cammuso C, Williams JL, Nims SD, Porter CA, Midura P, Palacios MJ, Ayres SL, Denniston RS, Hayes ML, Ziomek CA, Meade HM, Godke RA, Gavin WG, Overstrom EW, Echelard Y 1999 Production of goats by somatic cell nuclear transfer. Nat Biotechnol 17: 456–461
Keefer CL, Keyston R, Lazaris A, Bhatia B, Begin I, Bilodeau AS, Zhou FJ, Kafidi N, Wang B, Baldassarre H, Karatzas CN 2002 Production of cloned goats after nuclear transfer using adult somatic cells. Biol Reprod 66: 199–203
Wakayama T, Perry AC, Zuccotti M, Johnson KR, Yanagimachi R 1998 Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394: 369–374
Betthauser J, Forsberg E, Augenstein M, Childs L, Eilertsen K, Enos J, Forsythe T, Golueke P, Jurgella G, Koppang R, Lesmeister T, Mallon K, Mell G, Misica P, Pace M, Pfister-Genskow M, Strelchenko N, Voelker G, Watt S, Thompson S, Bishop M 2000 Production of cloned pigs from in vitro systems. Nat Biotechnol 18: 1055–1059
Polejaeva IA, Chen SH, Vaught TD, Page RL, Mullins J, Ball S, Dai Y, Boone J, Walker S, Ayares DL, Colman A, Campbell KH 2000 Cloned pigs produced by nuclear transfer from adult somatic cells. Nature 407: 86–90
Onishi A, Iwamoto M, Akita T, Mikawa S, Takeda K, Awata T, Hanada H, Perry AC 2000 Pig cloning by microinjection of fetal fibroblast nuclei. Science 289: 1188–1190
De Sousa PA, Dobrinsky JR, Zhu J, Archibald AL, Ainslie A, Bosma W, Bowering J, Bracken J, Ferrier PM, Fletcher J, Gasparrini B, Harkness L, Johnston P, Ritchie M, Ritchie WA, Travers A, Albertini D, Dinnyes A, King TJ, Wilmut I 2002 Somatic cell nuclear transfer in the pig: control of pronuclear formation and integration with improved methods for activation and maintenance of pregnancy. Biol Reprod 66: 642–650
Colman A, Kind A 2000 Therapeutic cloning: concepts and practicalities. Trends Biotechnol 18: 192–196
Vogelstein B, Alberts B, Shine K 2002 Genetics. Please don't call it cloning!. Science 295: 1237
Lanza RP, Chung HY, Yoo JJ, Wettstein PJ, Blackwell C, Borson N, Hofmeister E, Schuch G, Soker S, Moraes CT, West MD, Atala A 2002 Generation of histocompatible tissues using nuclear transplantation. Nat Biotechnol 20: 689–696
Humes HD, Buffington DA, MacKay SM, Funke AJ, Weitzel WF 1999 Replacement of renal function in uremic animals with a tissue-engineered kidney. Nat Biotechnol 17: 451–455
Amiel GE, Yoo JJ, Atala A 2000 Renal therapy using tissue-engineered constructs and gene delivery. World J Urol 18: 71–79
Steer DL, Nigam SK 2004 Developmental approaches to kidney tissue engineering. Am J Physiol Renal Physiol 286: F1–F7
Costantini F 2006 Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation 74: 402–421
Costantini F, Shakya R 2006 GDNF/Ret signaling and the development of the kidney. Bioessays 28: 117–127
Monte JC, Sakurai H, Bush KT, Nigam SK 2007 The developmental nephrome: systems biology in the developing kidney. Curr Opin Nephrol Hypertens 16: 3–9
Sampogna RV, Nigam SK 2004 Implications of gene networks for understanding resilience and vulnerability in the kidney branching program. Physiology (Bethesda) 19: 339–347
Shah MM, Sampogna RV, Sakurai H, Bush KT, Nigam SK 2004 Branching morphogenesis and kidney disease. Development 131: 1449–1462
Basson MA, Akbulut S, Watson-Johnson J, Simon R, Carroll TJ, Shakya R, Gross I, Martin GR, Lufkin T, McMahon AP, Wilson PD, Costantini FD, Mason IJ, Licht JD 2005 Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 8: 229–239
Basson MA, Watson-Johnson J, Shakya R, Akbulut S, Hyink D, Costantini FD, Wilson PD, Mason IJ, Licht JD 2006 Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 299: 466–477
Qiao J, Sakurai H, Nigam SK 1999 Branching morphogenesis independent of mesenchymal-epithelial contact in the developing kidney. Proc Natl Acad Sci USA 96: 7330–7335
Steer DL, Bush KT, Meyer TN, Schwesinger C, Nigam SK 2002 A strategy for in vitro propagation of rat nephrons. Kidney Int 62: 1958–1965
Rogers SA, Lowell JA, Hammerman NA, Hammerman MR 1998 Transplantation of developing metanephroi into adult rats. Kidney Int 54: 27–37
Rogers SA, Liapis H, Hammerman MR 2001 Transplantation of metanephroi across the major histocompatibility complex in rats. Am J Physiol Regul Integr Comp Physiol 280: R132–R136
Rogers SA, Hammerman MR 2001 Transplantation of rat metanephroi into mice. Am J Physiol Regul Integr Comp Physiol 280: R1865–R1869
Rogers SA, Hammerman MR 2001 Transplantation of metanephroi after preservation in vitro. Am J Physiol Regul Integr Comp Physiol 281: R661–R665
Rogers SA, Talcott M, Hammerman MR 2003 Transplantation of pig metanephroi. ASAIO J 49: 48–52
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Perin, L., Giuliani, S., Sedrakyan, S. et al. Stem Cell and Regenerative Science Applications in the Development of Bioengineering of Renal Tissue. Pediatr Res 63, 467–471 (2008). https://doi.org/10.1203/PDR.0b013e3181660653
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/PDR.0b013e3181660653
This article is cited by
-
Bioinformatics Approaches to Stem Cell Research
Current Pharmacology Reports (2018)
-
In-silico models of stem cell and developmental systems
Theoretical Biology and Medical Modelling (2014)
-
Illustration of extensive extracellular matrix at the epithelial-mesenchymal interface within the renal stem/progenitor cell niche
BMC Clinical Pathology (2012)
-
Peculiarities of the extracellular matrix in the interstitium of the renal stem/progenitor cell niche
Histochemistry and Cell Biology (2011)
-
In Vitro and In Vivo Cardiomyogenic Differentiation of Amniotic Fluid Stem Cells
Stem Cell Reviews and Reports (2011)