Current Stem Cell Reports

, Volume 3, Issue 2, pp 68–76 | Cite as

Bioartificial Kidneys

  • Peter R. Corridon
  • In Kap Ko
  • James J. YooEmail author
  • Anthony Atala
Artificial Tissues (A Atala and JG Hunsberger, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Artificial Tissues


Purpose of Review

Historically, there have been many advances in the ways in which we treat kidney diseases. In particular, hemodialysis has set the standard for treatment since the early 1960s and continues today as the most common form of treatment for acute, chronic, and end-stage conditions. However, the rising global prevalence of kidney diseases and our limited understanding of their etiologies have placed significant burdens on current clinical management regimens. This has resulted in a desperate need to improve the ways in which we treat the underlying and ensuing causes of kidney diseases for those who are unable to receive transplants.

Recent Findings

One way of possibly addressing these issues is through the use of improved bioartificial kidneys. Bioartificial kidneys provide an extension to conventional artificial kidneys and dialysis systems, by incorporating aspects of living cellular and tissue function, in an attempt to better mimic normal kidneys. Recent advancements in genomic, cellular, and tissue engineering technologies are facilitating the improved design of these systems.


In this review, we outline various research efforts that have focused on the development of regenerated organs, implantable constructs, and whole bioengineered kidneys, as well as the transitions from conventional dialysis to these novel alternatives. As a result, we envision that these pioneering efforts can one day produce bioartificial renal technologies that can either perform or reintroduce essential function, and thus provide practical options to treat and potentially prevent kidney diseases.


Bioratificial kidney Regenerative medicine Bioengineering Dialysis Cell therapy and gene therapy 


Compliance with Ethical Standards

Conflict of Interest

Peter R. Corridon has a patent pending on hydrodynamic methods for delivering fluids to kidney tissues and related materials and methods.

In Kap Ko, James J. Yoo, and Anthony Atala declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Stevens LA, Viswanathan G, Weiner DE. CKD and ESRD in the elderly: current prevalence, future projections, and clinical significance. Adv Chronic Kidney Dis. 2010;17(4):293–301.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ojo A. Addressing the global burden of chronic kidney disease through clinical and translational research. Trans Am Clin Climatol Assoc. 2014;125:229–46.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med. 2013;369(14):1336–43.CrossRefPubMedGoogle Scholar
  4. 4.
    Global Facts: About Kidney Disease [Internet]. The National Kidney Foundation. 2015 2016. Available from:
  5. 5.
    Kidney Disease Statistics for the United States [Internet]. 2016. Available from:
  6. 6.
    Ethiopia KP. Acute kidney injury: an overview [Internet]. 2016. Available from:
  7. 7.
    Abecassis M, Bartlett ST, Collins AJ, Davis CL, Delmonico FL, Friedewald JJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) conference. Clin J Am Soc Nephrol CJASN. 2008;3(2):471–80.CrossRefPubMedGoogle Scholar
  8. 8.
    Rosen L, Vining AR, Weimer DL. Addressing the shortage of kidneys for transplantation: purchase and allocation through chain auctions. J Health Polit Policy Law. 2011;36(4):717–55.CrossRefPubMedGoogle Scholar
  9. 9.
    Mallappallil M, Friedman EA, Delano BG, McFarlane SI, Salifu MO. Chronic kidney disease in the elderly: evaluation and management. Clin Pract Lond Engl. 2014;11(5):525–35.CrossRefGoogle Scholar
  10. 10.
    Chapman JR. What are the key challenges we face in kidney transplantation today? Transplant Res. 2013;2(1):1–7.CrossRefGoogle Scholar
  11. 11.
    Anderson S, Halter JB, Hazzard WR, Himmelfarb J, Horne FM, Kaysen GA, et al. Prediction, progression, and outcomes of chronic kidney disease in older adults. J Am Soc Nephrol. 2009;20(6):1199–209.CrossRefPubMedGoogle Scholar
  12. 12.
    Martin AB, Hartman M, Washington B, Catlin A, Team the NHEA. National Health Spending: Faster Growth In 2015 As Coverage Expands And Utilization Increases. Health Aff (Millwood). 2016 Dec 2; 10.1377/hlthaff.2016.1330.
  13. 13.
    Mason C, Dunnill P. The strong financial case for regenerative medicine and the regen industry. Regen Med. 2008;3(3):351–63.CrossRefPubMedGoogle Scholar
  14. 14.
    Bubela T, McCabe C, Archibald P, Atkins H, Bradshaw SE, Kefalas P, et al. Bringing regenerative medicines to the clinic: the future for regulation and reimbursement. Regen Med. 2015;10(7):897–911.CrossRefPubMedGoogle Scholar
  15. 15.
    Tasnim F, Deng R, Hu M, Liour S, Li Y, Ni M, et al. Achievements and challenges in bioartificial kidney development. Fibrogenesis Tissue Repair. 2010;3:14.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kim S, Fissell WH, Humes HD, Roy S. Current strategies and challenges in engineering a bioartificial kidney. Front Biosci Elite Ed. 2015;7:215–28.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Gura V, Rivara MB, Bieber S, Munshi R, Smith NC, Linke L, et al. A wearable artificial kidney for patients with end-stage renal disease. JCI Insight [Internet]. 2016. Fast Track, Breakthrough Therapy, Accelerated. 2016;1(8). Available from:
  18. 18.
    Brown PA, Bodles-Brakhop AM, Pope MA, Draghia-Akli R. Gene therapy by electroporation for the treatment of chronic renal failure in companion animals. BMC Biotechnol. 2009;9:4.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Parker T, Hakim R, Nissenson AR, Steinman T, Glassock RJ. Dialysis at a crossroads: 50 years later. Clin J Am Soc Nephrol. 2011;6(2):457–61.CrossRefPubMedGoogle Scholar
  20. 20.
    Szeto C-C. Peritonitis rates of the past thirty years: from improvement to stagnation. Perit Dial Int J Int Soc Perit Dial. 2014;34(2):151–3.CrossRefGoogle Scholar
  21. 21.
    Humes HD. Stem cells: the next therapeutic frontier. Trans Am Clin Climatol Assoc. 2005;116:167–84.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Fissell WH, Roy S, Davenport A. Achieving more frequent and longer dialysis for the majority: wearable dialysis and implantable artificial kidney devices. Kidney Int. 2013;84(2):256–64.CrossRefPubMedGoogle Scholar
  23. 23.
    Aebischer P, Ip TK, Panol G, Galletti PM. The bioartificial kidney: progress towards an ultrafiltration device with renal epithelial cells processing. Life Support Syst J Eur Soc Artif Organs. 1987;5(2):159–68.Google Scholar
  24. 24.
    Humes HD, Buffington D, Westover AJ, Roy S, Fissell WH. The bioartificial kidney: current status and future promise. Pediatr Nephrol. 2013;29(3):343–51.CrossRefPubMedGoogle Scholar
  25. 25.
    Song JH, Humes HD. The bioartificial kidney in the treatment of acute kidney injury. Curr Drug Targets. 2009;10(12):1227–34.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Commissioner O of the. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review [Internet]. 2017. Available from:
  27. 27.
    McCoy L. Artificial kidneys may start saving lives soon MedCareer News [Internet]. MedCareer News. 2015. 2016. Available from:
  28. 28.
    Beltz AD. Wearable, portable, light-weight artificial kidney [Internet]. US5284470 A, 1994 2017. Available from:
  29. 29.
    Chung HC, Ko IK, Atala A, Yoo JJ. Cell-based therapy for kidney disease. Korean J Urol. 2015;56(6):412–21.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ko IK, Lee SJ, Atala A, Yoo JJ. In situ tissue regeneration through host stem cell recruitment. Exp Mol Med. 2013;45(11):e57.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Gong R. Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease: targeting the inflamed vascular endothelium. J Am Soc Nephrol. 2006;17(9):2464–73.CrossRefPubMedGoogle Scholar
  32. 32.
    Homsi E, Janino P, Biswas SK, Mizuno S, Nakamura T, Lopes de Faria JB. Attenuation of glycerol-induced acute kidney injury by previous partial hepatectomy: role of hepatocyte growth factor/c-met axis in tubular protection. Nephron Exp Nephrol. 2007;107(3):e95–106.CrossRefPubMedGoogle Scholar
  33. 33.
    Sugimura K, Goto T, Tsuchida K, Takemoto Y, Kim T, Kishimoto T. Production and activation of hepatocyte growth factor in acute renal failure. Ren Fail. 2001;23(3–4):597–603.CrossRefPubMedGoogle Scholar
  34. 34.
    Tang J, Liu N, Zhuang S. Role of epidermal growth factor receptor in acute and chronic kidney injury. Kidney Int. 2013 May;83(5):804–10.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yen T-H, Alison MR, Goodlad RA, Otto WR, Jeffery R, Cook HT, et al. Epidermal growth factor attenuates tubular necrosis following mercuric chloride damage by regeneration of indigenous, not bone marrow-derived cells. J Cell Mol Med. 2015;19(2):463–73.CrossRefPubMedGoogle Scholar
  36. 36.
    Carley WW, Milici AJ, Madri JA. Extracellular matrix specificity for the differentiation of capillary endothelial cells. Exp Cell Res. 1988;178(2):426–34.CrossRefPubMedGoogle Scholar
  37. 37.
    Moon KH, Ko IK, Yoo JJ, Atala A. Kidney diseases and tissue engineering. Methods San Diego Calif. 2016;99:112–9.CrossRefGoogle Scholar
  38. 38.
    Serum and urinary insulin-like growth factor-1 and tumor necrosis factor in neonates with and without acute renal failure—ProQuest [Internet]. 2016. Available from:
  39. 39.
    Bach LA, Hale LJ. Insulin-like growth factors and kidney disease. Am J Kidney Dis Off J Natl Kidney Found. 2015 Feb;65(2):327–36.CrossRefGoogle Scholar
  40. 40.
    Kopple JD, Massry SG. Kopple and Massry’s Nutritional Management of Renal Disease. Lippincott Williams & Wilkins; 2004. 712 p.Google Scholar
  41. 41.
    •• Corridon PR, Rhodes GJ, Leonard EC, Basile DP, Gattone VH, Bacallao RL, et al. A method to facilitate and monitor expression of exogenous genes in the rat kidney using plasmid and viral vectors. Am J Physiol Renal Physiol. 2013;304(9):F1217–29. This method can serve to reduce the barriers to preclinical assessments of clinical interventions related to the kidney.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wynn R. Stem cell transplantation in inherited metabolic disorders. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2011;2011:285–91.Google Scholar
  43. 43.
    Corridon P, Rhodes G, Zhang S, Bready D, Xu W, Witzmann F, et al. Hydrodynamic delivery of mitochondrial genes in vivo protects against moderate ischemia-reperfusion injury in the rat kidney (690.17). FASEB J. 28(1 Supplement):690.17.Google Scholar
  44. 44.
    Merta M, Kohoutová M, Rysavá R. Perspectives in gene therapy of polycystic kidney disease. Sb Lek. 1999;100(4):259–68.PubMedGoogle Scholar
  45. 45.
    Torres VE, Harris PC. Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases. Nat Clin Pract Nephrol. 2006;2(1):40–55.CrossRefPubMedGoogle Scholar
  46. 46.
    Freedman BS. Modeling kidney disease with iPS cells. Biomark Insights. 2015;10(Suppl 1):153–69.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Huang JL, Woolf AS, Kolatsi-Joannou M, Baluk P, Sandford RN, Peters DJM, et al. Vascular endothelial growth factor C for polycystic kidney diseases. J Am Soc Nephrol. 2015 ;ASN.2014090856.Google Scholar
  48. 48.
    Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice. Publ Online 21 Sept 2001 Doi101038sjgt3301545 [Internet]. 2001 21 [cited 2016 Oct 10];8(19). Available from:
  49. 49.
    Dai C, Yang J, Liu Y. Single injection of naked plasmid encoding hepatocyte growth factor prevents cell death and ameliorates acute renal failure in mice. J Am Soc Nephrol JASN. 2002;13(2):411–22.PubMedGoogle Scholar
  50. 50.
    Anders H-J, Rovin B, Jayne D, Brunetta P, Coppo R, Davidson A, et al. ISN Nexus 2016 Symposia: translational immunology in kidney disease—the berlin roadmap. Kidney Int Rep. 2016;1(4):327–39.CrossRefGoogle Scholar
  51. 51.
    Maeshima A, Nakasatomi M, Nojima Y. Regenerative medicine for the kidney: renotropic factors, renal stem/progenitor cells, and stem cell therapy. BioMed Res Int [Internet]. 2014 [cited 2016 10];2014. Available from:
  52. 52.
    Chung HC, Ko IK, Atala A, Yoo JJ. Cell-based therapy for kidney disease. Korean J Urol. 2015;56(6):412–21.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Chou Y-H, Pan S-Y, Yang C-H, Lin S-L. Stem cells and kidney regeneration. J Formos Med Assoc. 2014;113(4):201–9.CrossRefPubMedGoogle Scholar
  54. 54.
    Lin F. Stem cells in kidney regeneration following acute renal injury. Pediatr Res. 2006;59(S4):74R–8R.CrossRefPubMedGoogle Scholar
  55. 55.
    Lee S-R, Lee S-H, Moon J-Y, Park J-Y, Lee D, Lim SJ, et al. Repeated administration of bone marrow-derived mesenchymal stem cells improved the protective effects on a remnant kidney model. Ren Fail. 2010;32(7):840–8.CrossRefPubMedGoogle Scholar
  56. 56.
    Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, Di Primio R. Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells. Int J Immunopathol Pharmacol. 2008;21(3):595–602.CrossRefPubMedGoogle Scholar
  57. 57.
    Gholizadeh-Ghalehaziz S, Farahzadi R, Fathi E, Pashaiasl M. A mini overview of isolation, characterization and application of amniotic fluid stem cells. Int J Stem Cells. 2015;8(2):115–20.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Nakamura M, Okano H. Cell transplantation therapies for spinal cord injury focusing on induced pluripotent stem cells. Cell Res. 2013;23(1):70–80.CrossRefPubMedGoogle Scholar
  59. 59.
    Arenas-Herrera JE, Ko IK, Atala A, Yoo JJ. Decellularization for whole organ bioengineering. Biomed Mater Bristol Engl. 2013;8(1):14106.CrossRefGoogle Scholar
  60. 60.
    Kim I-H, Ko IK, Atala A, Yoo JJ. Whole kidney engineering for clinical translation. Curr Opin Organ Transplant. 2015;20(2):165–70.CrossRefPubMedGoogle Scholar
  61. 61.
    Scarritt ME, Pashos NC, Bunnell BA. A review of cellularization strategies for tissue engineering of whole organs. Front Bioeng Biotechnol [Internet]. 2015 30 [cited 2016 Sep 30];3. Available from:
  62. 62.
    Song JJ, Ott HC. Organ engineering based on decellularized matrix scaffolds. Trends Mol Med. 2011;17(8):424–32.CrossRefPubMedGoogle Scholar
  63. 63.
    • Madariaga MLL, Ott HC. Bioengineering kidneys for transplantation. Semin Nephrol. 2014;34(4):384–93. This study provides thorough descriptions of key elements need to support the development of bioengineered kidneys.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Guyette JP, Charest JM, Mills RW, Jank BJ, Moser PT, Gilpin SE, et al. Bioengineering human myocardium on native extracellular matrixnovelty and significance. Circ Res. 2016;118(1):56–72.CrossRefPubMedGoogle Scholar
  65. 65.
    Cooper TP, Sefton MV. Fibronectin coating of collagen modules increases in vivo HUVEC survival and vessel formation in SCID mice. Acta Biomater. 2011;7(3):1072–83.CrossRefPubMedGoogle Scholar
  66. 66.
    Corstorphine L, Sefton MV. Effectiveness factor and diffusion limitations in collagen gel modules containing HepG2 cells. J Tissue Eng Regen Med. 2011;5(2):119–29.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Peter R. Corridon
    • 1
    • 2
    • 3
  • In Kap Ko
    • 1
  • James J. Yoo
    • 1
    Email author
  • Anthony Atala
    • 1
  1. 1.Wake Forest Institute for Regenerative MedicineWinston-SalemUSA
  2. 2.Department of Physiology & PharmacologyWake Forest School of MedicineWinston-SalemUSA
  3. 3.Department of Craniofacial BiologyUniversity of Colorado, Anschutz Medical CampusAuroraUSA

Personalised recommendations