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Repopulation of decellularized whole organ scaffold using stem cells: an emerging technology for the development of neo-organ

  • Review
  • Tissue Engineering / Regenerative Medicine
  • Published:
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Abstract

Demand of donor organs for transplantation in treatment of organ failure is increasing. Hence there is a need to develop new strategies for the alternative sources of organ development. Attempts are being made to use xenogenic organs by genetic manipulation but the organ rejection against human always has been a major challenge for the survival of the graft. Advancement in the genetic bioengineering and combination of different allied sciences for the development of humanized organ system, the therapeutic influence of stem cell fraction on the reconstitution of organ architecture and their regenerative abilities in different tissues and organs provides a better approach to solve the problem of organ shortage. However, the available strategies for generating the organ/tissue scaffolds limit its application due to the absence of complete three-dimensional (3D) organ architecture, mechanical strength, long-term cell survival, and vascularization. Repopulation of whole decellularized organ scaffolds using stem cells has added a new dimension for creating new bioengineered organs. In recent years, several studies have demonstrated the potential application of decellularization and recellularization approach for the development of functional bio-artificial organs. With the help of established procedures for conditioning, extensive stem cells and organ engineering experiments/transplants for the development of humanized organs will allow its preclinical evaluation for organ regeneration before translation to the clinic. This review focuses on the major aspects of organ scaffold generation and repopulation of different types of whole decellularized organ scaffolds using stem cells for the functional benefit and their confines.

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References

  1. Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA. 1985;254:3321–9.

    Article  CAS  PubMed  Google Scholar 

  2. Lan C, Xiao W, Xiao-Hui D, Chun-Yan H, Hong-Ling Y. Tissue culture before transplantation of frozen–thawed human fetal ovarian tissue into immunodeficient mice. Fertil Steril. 2010;93:913–9.

    Article  PubMed  Google Scholar 

  3. Van Eyck AS, Bouzin C, Feron O, Romeu L, Van Langendonckt A, Donnez J, Dolmans MM. Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model. Fertil Steril. 2010;93:1676–85.

    Article  PubMed  Google Scholar 

  4. Baksh D, Davies E, Kim S. Three-dimensional matrices of calcium polyphosphates support bone growth in vitro and in vivo. J Mater Sci. 1998;9:743.

    CAS  Google Scholar 

  5. Ishaug SL, Crane GM, Miller J, et al. Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds. J Biomed Mater Res. 1997;36:17.

    Article  CAS  PubMed  Google Scholar 

  6. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14:213–21.

    Article  CAS  PubMed  Google Scholar 

  7. Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, Ddson A, Martorell J, Bellini S, Parnigotto PP, Dickinson SC, Hollander AP, Mantero S, Conconi MR, Birchall MA. Clinical transplantation of a tissue-engineered airway. Lancet. 2008;372:2023–30.

    Article  PubMed  Google Scholar 

  8. Hollander A, Macchiarini P, Gordijn B, Birchall M. The first stem cell-based tissue-engineered organ replacement: implications for regenerative medicine and society. Regen Med. 2009;4:147–8.

    Article  PubMed  Google Scholar 

  9. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE. Generation of a functional mammary gland from a single stem cell. Nat. 2006;439:84–8.

    Article  CAS  Google Scholar 

  10. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI. Eaves purification and unique properties of mammary epithelial stem cells. Nat. 2006;439:993–7.

    CAS  Google Scholar 

  11. Leong KG, Wang BE, Johnson L, Gao WQ. Generation of a prostate from a single adult stem cell. Nat. 2008;456:804–8.

    Article  CAS  Google Scholar 

  12. Chen J, Lansford R, Stewart V, Young F, Alt FW. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc Natl Acad Sci USA. 1993;90:4528–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Kobayashi T, Yamaguchi T, Hamanaka S, Kato-Itoh M, Yamazaki Y, Ibata M, Sato H, Lee YS, Usui J, Knisely AS, Hirabayashi M, Nakauchi H. Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell. 2010;142:787–99.

    Article  CAS  PubMed  Google Scholar 

  14. Cao Y, Vacanti JP, Paige KT, Upton J, Vacanti CA. Transplantation of chondrocytes utilizing a polymer-cell construct to produce tissue-engineered cartilage in the shape of a human ear. Plast Reconstr Surg. 1997;100:297–302.

    Article  CAS  PubMed  Google Scholar 

  15. Takebe T, Koike N, Sekine K, Enomura M, Chiba Y, Ueno Y, Zheng YW, Taniguchi H. Generation of functional human vascular network. Transpl Proc. 2012;44:1130–3.

    Article  CAS  Google Scholar 

  16. Badylak SF, Taylor D, Uygun K. Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Ann Rev Biomed Eng. 2011;13:27–53.

    Article  CAS  Google Scholar 

  17. Baptista PM, Orlando G, Mirmalek-Sani SH, Siddiqui M, Atala A, Soker S. Whole organ decellularization: a tool for bioscaffold fabrication and organ bioengineering. Conf Proc IEEE Eng Med Biol Soc. 2009;65:26–9.

    Google Scholar 

  18. Habibullah CM, Vijayalakshmi V, Naseem B, Habeeb MH, Shashi S, Rao M. Hepatofunctional study of UV-B (302 nm) irradiated goat hepatocytes. Am J Gastroenterol. 2000;95:2511–2.

    Article  Google Scholar 

  19. Khan AA, Capoor AK, Parveen N, Naseem S, Vijayalakshmi V, Venkateshan V, Habibullah CM. In vitro studies on a bioreactor module containing encapsulated goat hepatocytes for the development of bioartificial liver. Ind J Gastroenterol. 2002;21:55–8.

    Google Scholar 

  20. Ross EA, Abrahamson DR, John PL, Clapp WL, Williams MJ, et al. Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes. Organogen. 2012;8:49–55.

    Article  Google Scholar 

  21. Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19:1–8.

    Article  Google Scholar 

  22. Nakayama KH, Lee CCI, Batchelder CA, Tarantal AF. Tissue specificity of decellularized rhesus monkey kidney and lung scaffolds. PLoS One. 2013;8:e64134.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Bowen J. By the numbers: heart transplants in the US. WSFA stories. (Online Statistics) 2012.

  24. Ng SL, Narayanan K, Gao S, Wan AC. Lineage restricted progenitors for the repopulation of decellularized heart. Biomat. 2011;32:7571–80.

    Article  CAS  Google Scholar 

  25. Lu TY, Lin B, Kim J, Sullivan M, Tobita K, Salama G, Yang L. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun. 2013;4:2307.

    PubMed  Google Scholar 

  26. Zacchi V, Soranzo C, Cortivo R, Radice M, Brun P, Abatangelo G. In vitro engineering of human skin-like tissue. J Biomed Mater Res. 1998;40:187–94.

    Article  CAS  PubMed  Google Scholar 

  27. Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med. 2001;7:1035–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB. Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet. 2006;367:1241–6.

    Article  PubMed  Google Scholar 

  29. Griffith LG, Naughton G. Tissue engineering—current challenges and expanding opportunities. Sci. 2002;295:1009–14.

    Article  CAS  Google Scholar 

  30. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatol. 2011;53:604–17.

    Article  CAS  Google Scholar 

  31. Kawai T, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;358:353–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Rogers SA, Hammerman MR. Prolongation of life in anephric rats following de novo renal organogenesis. Organogen. 2004;1:22–5.

    Article  Google Scholar 

  33. Gura V, Macy AS, Beizai M, Ezon C, Golper TA. Technical breakthroughs in the wearable artificial kidney (WAK). Clin J Am Soc Nephrol. 2009;4:1441–8.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Fissell WH, Roy S. The implantable artificial kidney. Semin Dial. 2009;22:665–70.

    Article  PubMed  Google Scholar 

  35. Lopez AD, Shibuya K, Rao C, et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur Respir J. 2006;27:397–412.

    Article  CAS  PubMed  Google Scholar 

  36. Eisner MD, Anthonisen N, Coultas D, et al. An official American thoracic society public policy statement: novel risk factors and the global burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010;182:693–718.

    Article  PubMed  Google Scholar 

  37. Cortiella J, Niles J, Cantu A, et al. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation. Tissue Eng Part A. 2010;16:2565–80.

    Article  CAS  PubMed  Google Scholar 

  38. Petersen TH, et al. Tissue-engineered lungs for in vivo implantation. Sci. 2010;329:538–41.

    Article  CAS  Google Scholar 

  39. Price AP, England KA, et al. Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. Tissue Eng Part A. 2010;16:2581–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Petersen TH, Calle EA, Colehour MB, et al. Matrix composition and mechanics of decellularized lung scaffolds. Cells Tissue Org. 2012;195:222–31.

    Article  CAS  Google Scholar 

  41. Osada H, Takeuchi S, Kojima K, Yamate N. The first step of experimental study on hybrid trachea: use of cultured fibroblasts with artificial matrix. J Cardiovasc Surg (Torino). 1994;35:165–8.

    CAS  Google Scholar 

  42. Vacanti CA, Paige KT, Kim WS, Sakata J, Upton J, et al. Experimental tracheal replacement using tissue-engineered cartilage. J Pediatr Surg. 1994;29:201–4.

    Article  CAS  PubMed  Google Scholar 

  43. Paz AC, Kojima K, Iwasaki K, Ross JD, Canseco JA, et al. Tissue engineered trachea using decellularized aorta. J Bioeng Biomed Sci. 2011;S2:001.

    Google Scholar 

  44. DeQuach JA, et al. Simple and high yielding method for preparing tissue specific extracellular matrix coatings for cell culture. PLoS One. 2010;5:e13039.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, Kotton D, Vacanti JP. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010;16:927–33.

    Article  CAS  PubMed  Google Scholar 

  46. Brown BN, Freund JM, Han LI, Rubin JP, Reing JE, et al. Comparison of three methods for the derivation of a biological scaffold composed of adipose tissue extracellular matrix. Tissue Eng. 2011;17:411–21.

    Article  CAS  Google Scholar 

  47. Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomat. 2006;27:3675–83.

    CAS  Google Scholar 

  48. Gupta SK, Dinda AK, Potdar PD, Mishra NC. Modification of decellularized goat-lung scaffold with chitosan/nanohydroxyapatite composite for bone tissue engineering applications. BioMed Res Internat 2013;2013:1–11.

    Article  Google Scholar 

  49. Sano MB, Neal RE, Garcia PA, Gerber D, Robertson J, Davalos RV. Towards the creation of decellularized organ constructs using irreversible electroporation and active mechanical perfusion. Biomed Eng Online. 2010;9:83.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Shupe T, Williams M, Brown A, Willenberg B, Petersen BE. Methods for the decellularization of intact rat liver. Organogen. 2010;6:134–6.

    Article  Google Scholar 

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Authors and Affiliations

  1. Centre for Liver Research and Diagnostics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, India

    Aleem Ahmed Khan, Sandeep Kumar Vishwakarma & Avinash Bardia

  2. Department of Radiology, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, India

    J. Venkateshwarulu

  3. Salar-E-Millat Research Centre, Princess Esra Hospital, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, 500 058, Andhra Pradesh, India

    Aleem Ahmed Khan

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  1. Aleem Ahmed Khan
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Correspondence to Aleem Ahmed Khan.

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Khan, A.A., Vishwakarma, S.K., Bardia, A. et al. Repopulation of decellularized whole organ scaffold using stem cells: an emerging technology for the development of neo-organ. J Artif Organs 17, 291–300 (2014). https://doi.org/10.1007/s10047-014-0780-2

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  • DOI: https://doi.org/10.1007/s10047-014-0780-2

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