End-stage organ disease affects millions of people around the world, to whom organ
transplantation is the only definitive cure available. However, persistent organ shortage
and the resulting widespread transplant backlog are part of a disturbing reality and
a common burden felt by thousands of patients on waiting lists in almost every country
where organ transplants are performed. Several alternatives and potential solutions
to this problem have been sought in past decades, but one seems particularly promising
now: whole-organ bioengineering. This review describes briefly the evolution of organ
transplantation and the development of decellularized organ scaffolds and their application
to organ bioengineering. This modern alchemy of generating whole-organ scaffolds and
recellularizing them with multiple cell types in perfusion bioreactors is paving the
way for a new revolution in transplantation medicine. Furthermore, although the first
generation of bioengineered organs still lacks true clinical value, it has created
a number of novel tissue and organ model platforms with direct application in other
areas of science (eg, developmental biology and stem cell biology, drug discovery,
physiology and metabolism). In this review, we describe the current status and numerous
applications of whole-organ bioengineering, focusing also on the multiple challenges
that researchers have to overcome to translate these novel technologies fully into
transplantation medicine.
Abbreviations:
ECM (extracellular matrix), hESC (human embryonic stem cell), mESC (murine embryonic stem cell), TESI (tissue-engineered small intestine)To read this article in full you will need to make a payment
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References
- Successful homotransplantation of the kidney in an identical twin.Trans Am Clin Climatol Assoc. 1955; 67: 167-173
- Transplantation: a medical miracle of the 20th century.N Engl J Medicine. 2004; 351: 2678-2680
- Cyclosporin A in patients receiving renal allografts from cadaver donors.Lancet. 1978; ii: 1323-1327
- Prolongation of allograft survival by cyclosporin A.Surg Forum. 1979; 30: 287-289
- The use of cyclosporin A immunosuppression in organ grafting.Immunol Rev. 1982; 65: 115-131
- Cyclosporine: a new immunosuppressive agent for organ transplantation.Ann Intern Med. 1984; 101: 667-682
- History of solid organ transplantation and organ donation.Crit Care Clin. 2009; 25: 165-184
- Organs from animals for man.Int Arch Allergy Immunol. 1998; 116: 5-21
Sharing UNFO., Vol. 2013. Available at: http://optn.transplant.hrsa.gov.
- OPTN/SRTR 2011 annual data report: deceased organ donation.Am J Transplant. 2013; 13: 179-198
- OPTN/SRTR 2011 Annual data report: international data.Am J Transplant. 2013; 13: 199-225
Eurotransplant. Vol. 2013. Available at: http://www.eurotransplant.org/cms/.
- Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart.Nat Med. 2008; 14: 213-221
- Whole organ decellularization: a tool for bioscaffold fabrication and organ bioengineering.Conf Proc IEEE Eng Med Biol Soc. 2009; 2009: 6526-6529
- Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix.Nat Med. 2010; 16: 814-820
- The use of whole organ decellularization for the generation of a vascularized liver organoid.Hepatology. 2011; 53: 604-617
- A whole-organ regenerative medicine approach for liver replacement.Tissue Eng Part C Methods. 2011; 17: 677-686
- Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds.Hepatology. 2011; 53: 293-305
Duncan AW Soto-Gutierrez A. Liver repopulation and regeneration: new approaches to old questions. Curr Opin Organ Transplant 2013 18:197–202.
- Bioengineering in organ transplantation: targeting the liver.Transplant Proc. 2011; 43: 2137-2138
- Application of whole-organ tissue engineering in hepatology.Nat Rev Gastroenterol Hepatol. 2012; 9: 738-744
- Cellular therapy and bioartificial approaches to liver replacement.Curr Opin Organ Transplant. 2012; 17: 235-240
- Cell and organ bioengineering technology as applied to gastrointestinal diseases.Gut. 2013; 62: 774-786
- Tissue-engineering of the gastrointestinal tract.Curr Opin Pediatr. 2012; 24: 365-370
- Tissue-engineered small intestine improves recovery after massive small bowel resection.Ann Surg. 2004; 240: 748-754
- Biocompatibility and potential of decellularized porcine small intestine to support cellular attachment and growth.J Tissue Eng Regen Med. 2013; 1750
- Systemic decellularization for multi-organ scaffolds in rats.Transplant Proc. 2012; 44: 1151-1154
- Recellularization of acellular human small intestine using bone marrow stem cells.Stem Cells Transl Med. 2013; 2: 307-315
- A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration.Biomaterials. 2012; 33: 3401-3410
OPTN (Organ Procurement and Transplantation Network, 2012).
- Life-sparing effect of human cord blood: mesenchymal stem cells in experimental acute kidney injury.Stem Cells. 2010; 28: 513-522
- Regeneration and experimental orthotopic transplantation of a bioengineered kidney.Nat Med. 2013; 19: 646-651
- Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds.J Am Soc Nephrol. 2009; 20: 2338-2347
- Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes.Organogenesis. 2012; 8: 49-55
- Production and implantation of renal extracellular matrix scaffolds from porcine kidneys as a platform for renal bioengineering investigations.Ann Surg. 2012; 256
- Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system.Biomaterials. 2012; 33: 7756-7764
- Tissue specificity of decellularized rhesus monkey kidney and lung scaffolds.PLoS One. 2013; 8: 1-10
- Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering.Tissue Eng Part A. 2010; 16: 2207-2216
- Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.Biomaterials. 2013; 34: 5915-5925
- Deaths: Preliminary Data for 2010.National Vital Statistics Reports. 2012; 60
- Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.Nat Med. 2006; 12: 452-458
- Preparation of cardiac extracellular matrix from an intact porcine heart.Tissue Eng Part C Methods. 2010; 16: 525-532
- Preparation of cardiac extracellular matrix scaffolds by decellularization of human myocardium.J Biomed Mater Res A. 2013;
- Lineage restricted progenitors for the repopulation of decellularized heart.Biomaterials. 2011; 32: 7571-7580
- Global estimates of the prevalence of diabetes for 2010 and 2030.Diabetes Res Clin Pract. 2010; 87: 4-14
- Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering.Biomaterials. 2013; 34: 5488-5495
- Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering.Biomaterials. 2013; 34: 6760-6772
- Islet transplantation and encapsulation: an update on recent developments.Rev Diabet Stud. 2011; 8: 51-67
- Design of a bioartificial pancreas.J Invest Med. 2010; 58: 831-837
- Bioengineering the lung: molecules, materials, matrix, morphology, and mechanics.Am J Physiol Lung Cell Mol Physiol. 2012; 302: L361-L362
- Regeneration and orthotopic transplantation of a bioartificial lung.Nat Med. 2010; 16: 927-933
- Tissue-engineered lungs for in vivo implantation.Science. 2010; 329: 538-541
- Enhanced in vivo function of bioartificial lungs in rats.Ann Thorac Surg. 2011; 92: 998-1006
- Decellularization of human and porcine lung tissues for pulmonary tissue engineering.Ann Thorac Surg. 2013; 96: 1046-1056
- Regenerative medicine and developmental biology: the role of the extracellular matrix.Anat Rec Part B. 2005; 287: 36-41
- Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine.J Am Soc Nephrol. 2004; 15: 1113-1125
- Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds.Annu Rev Biomed Eng. 2011; 13: 27-53
- Stem cell differentiation and expansion for clinical applications of tissue engineering.J Cell Mol Med. 2007; 11: 935-944
- Systems for therapeutic angiogenesis in tissue engineering.World J Urol. 2000; 18: 10-18
- Vascularization in tissue engineering.Trends Biotechnol. 2008; 26: 434-441
- An overview of tissue and whole organ decellularization processes.Biomaterials. 2011; 32: 3233-3243
- The pivotal role of vascularization in tissue engineering.Annu Rev Biomed Eng. 2013; 15: 177-200
- Bioreactor design for perfusion-based, highly-vascularized organ regeneration.Curr Opin Chem Eng. 2013; 2: 32-40
- Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded.Tissue Eng Part A. 2010; 16: 2581-2591
- The role of bioreactors in tissue engineering.Trends Biotechnol. 2004; 22: 80-86
- Will the pig solve the transplantation backlog?.Annu Rev Med. 2002; 53: 133-147
- Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the United States.Tissue Eng Part B Rev. 2010; 16: 41-54
- Cardiac decellularisation with long-term storage and repopulation with canine peripheral blood progenitor cells.Can J Chem Eng. 2012; 90: 1457-1464
Article info
Publication history
Published online: January 13, 2014
Accepted:
January 6,
2014
Received:
December 18,
2013
Footnotes
E. Moran, A. Dhal, and D. Vyas contributed equally to this work.
Identification
Copyright
© 2014 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
