Chapter 3 – Whole-Organ Bioengineering—Current Tales of Modern Alchemy

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. Several alternatives and potential solutions to this problem have been sought in the past decades, but one seems particularly promising now, whole-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. In this chapter, we describe the present status and numerous applications of whole-organ bioengineering, focusing also in the multiple challenges that researchers have to overcome to fully translate these novel technologies into transplantation medicine.

[1]  H. Yagi,et al.  Bioengineering in organ transplantation: targeting the liver. , 2011, Transplantation proceedings.

[2]  Korkut Uygun,et al.  Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. , 2011, Annual review of biomedical engineering.

[3]  D. Wendt,et al.  The role of bioreactors in tissue engineering. , 2004, Trends in biotechnology.

[4]  T. Strom,et al.  Cyclosporine: a new immunosuppressive agent for organ transplantation. , 1984, Annals of internal medicine.

[5]  Doris A Taylor,et al.  Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart , 2008, Nature Medicine.

[6]  Pedro M. Baptista,et al.  The use of whole organ decellularization for the generation of a vascularized liver organoid , 2011, Hepatology.

[7]  Yunfang Wang,et al.  Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue‐specific biomatrix scaffolds , 2011, Hepatology.

[8]  M. Diefenbeck,et al.  Organs from Animals for Man , 1998, International Archives of Allergy and Immunology.

[9]  Angela Panoskaltsis-Mortari,et al.  Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. , 2010, Tissue engineering. Part A.

[10]  Karthikeyan Narayanan,et al.  Lineage restricted progenitors for the repopulation of decellularized heart. , 2011, Biomaterials.

[11]  Ashok Srinivasan,et al.  Tissue-Engineered Small Intestine Improves Recovery After Massive Small Bowel Resection , 2004, Annals of surgery.

[12]  Sandeep T. Koshy,et al.  Cardiac Decellularisation With Long-Term Storage and Repopulation With Canine Peripheral Blood Progenitor Cells †,‡ , 2012 .

[13]  J. Guyette,et al.  Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney , 2013, Nature Medicine.

[14]  P. Linden.  History of solid organ transplantation and organ donation. , 2009, Critical care clinics.

[15]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[16]  Donald O Freytes,et al.  Preparation of cardiac extracellular matrix from an intact porcine heart. , 2010, Tissue engineering. Part C, Methods.

[17]  Stephen F Badylak,et al.  An overview of tissue and whole organ decellularization processes. , 2011, Biomaterials.

[18]  G. Vunjak‐Novakovic,et al.  Decellularization of human and porcine lung tissues for pulmonary tissue engineering. , 2013, The Annals of thoracic surgery.

[19]  P. Morris.  Transplantation--a medical miracle of the 20th century. , 2004, The New England journal of medicine.

[20]  D. Sachs,et al.  Will the pig solve the transplantation backlog? , 2002, Annual review of medicine.

[21]  Christian Schuetz,et al.  Regeneration and orthotopic transplantation of a bioartificial lung , 2010, Nature Medicine.

[22]  W. Cui,et al.  Stem cell differentiation and expansion for clinical applications of tissue engineering , 2007, Journal of Cellular and Molecular Medicine.

[23]  A. Anwar,et al.  Bioengineering the Lung : Molecules , Materials , Matrix , Morphology , and Mechanics Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension , 2012 .

[24]  A. Israni,et al.  OPTN/SRTR 2011 Annual Data Report: International Data , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[25]  Mark Turmaine,et al.  Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies. , 2013, Biomaterials.

[26]  D. Dunn,et al.  CYCLOSPORIN A IN PATIENTS RECEIVING RENAL ALLOGRAFTS FROM CADAVER DONORS , 1978, The Lancet.

[27]  W. Miller,et al.  Bioreactor design for perfusion-based, highly-vascularized organ regeneration. , 2013, Current opinion in chemical engineering.

[28]  Mark F. Lythgoe,et al.  A rat decellularized small bowel scaffold that preserves villus-crypt architecture for intestinal regeneration , 2012, Biomaterials.

[29]  Martin L. Yarmush,et al.  Application of whole-organ tissue engineering in hepatology , 2012, Nature Reviews Gastroenterology &Hepatology.

[30]  R. Calne,et al.  The Use of Cyclosporin A Immunosuppression in Organ Grafting , 1982, Immunological reviews.

[31]  Karina H. Nakayama,et al.  Tissue Specificity of Decellularized Rhesus Monkey Kidney and Lung Scaffolds , 2013, PloS one.

[32]  Stephen F Badylak,et al.  Regenerative medicine and developmental biology: the role of the extracellular matrix. , 2005, Anatomical record. Part B, New anatomist.

[33]  F. Auger,et al.  The pivotal role of vascularization in tissue engineering. , 2013, Annual review of biomedical engineering.

[34]  A. Duncan,et al.  Liver repopulation and regeneration: new approaches to old questions , 2013, Current opinion in organ transplantation.

[35]  B. Sicari,et al.  Perfusion-decellularized pancreas as a natural 3D scaffold for pancreatic tissue and whole organ engineering. , 2013, Biomaterials.

[36]  T. Ansari,et al.  Biocompatibility and potential of decellularized porcine small intestine to support cellular attachment and growth , 2016, Journal of tissue engineering and regenerative medicine.

[37]  Zhen W. Zhuang,et al.  Tissue-Engineered Lungs for in Vivo Implantation , 2010, Science.

[38]  Christopher D. Batich,et al.  Mouse stem cells seeded into decellularized rat kidney scaffolds endothelialize and remodel basement membranes , 2012, Organogenesis.

[39]  Karina H Nakayama,et al.  Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. , 2010, Tissue engineering. Part A.

[40]  K. M. Park,et al.  Systemic decellularization for multi-organ scaffolds in rats. , 2012, Transplantation proceedings.

[41]  Steven S. Oh,et al.  Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the United States. , 2010, Tissue engineering. Part B, Reviews.

[42]  Petra Anić,et al.  Preparation of cardiac extracellular matrix scaffolds by decellularization of human myocardium. , 2013, Journal of biomedical materials research. Part A.

[43]  Pedro M. Baptista,et al.  Cellular therapy and bioartificial approaches to liver replacement , 2012, Current opinion in organ transplantation.

[44]  Andreas Hess,et al.  Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts , 2006, Nature Medicine.

[45]  M. Olausson,et al.  Retracted: Recellularization of Acellular Human Small Intestine Using Bone Marrow Stem Cells , 2013, Stem cells translational medicine.

[46]  Anthony Atala,et al.  Decellularization methods of porcine kidneys for whole organ engineering using a high-throughput system. , 2012, Biomaterials.

[47]  J. Shaw,et al.  Global estimates of the prevalence of diabetes for 2010 and 2030. , 2010, Diabetes research and clinical practice.

[48]  Naohiro Terada,et al.  Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. , 2009, Journal of the American Society of Nephrology : JASN.

[49]  John P McQuilling,et al.  Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering. , 2013, Biomaterials.

[50]  H. Ott,et al.  Enhanced in vivo function of bioartificial lungs in rats. , 2011, The Annals of thoracic surgery.

[51]  Stephen F Badylak,et al.  A whole-organ regenerative medicine approach for liver replacement. , 2011, Tissue engineering. Part C, Methods.

[52]  S. Soker,et al.  Cell and organ bioengineering technology as applied to gastrointestinal diseases , 2012, Gut.

[53]  Anthony Atala,et al.  Tissue engineering, stem cells, and cloning: opportunities for regenerative medicine. , 2004, Journal of the American Society of Nephrology : JASN.

[54]  Paolo De Coppi,et al.  Production and Implantation of Renal Extracellular Matrix Scaffolds From Porcine Kidneys as a Platform for Renal Bioengineering Investigations , 2012, Annals of surgery.

[55]  T. Grikscheit,et al.  Tissue-engineering of the gastrointestinal tract , 2012, Current opinion in pediatrics.

[56]  Hiroshi Yagi,et al.  Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix , 2010, Nature Medicine.

[57]  A. Israni,et al.  OPTN/SRTR 2011 Annual Data Report: Deceased Organ Donation , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[58]  O. Khanna,et al.  Design of a Bioartificial Pancreas+ , 2010, Journal of Investigative Medicine.

[59]  Anthony Atala,et al.  Systems for therapeutic angiogenesis in tissue engineering , 2000, World Journal of Urology.