Development of decellularized scaffolds for stem cell‐driven tissue engineering

Organ transplantation is an effective treatment for chronic organ dysfunctioning conditions. However, a dearth of available donor organs for transplantation leads to the death of numerous patients waiting for a suitable organ donor. The potential of decellularized scaffolds, derived from native tissues or organs in the form of scaffolds has been evolved as a promising approach in tissue‐regenerative medicine for translating functional organ replacements. In recent years, donor organs, such as heart, liver, lung and kidneys, have been reported to provide acellular extracellular matrix (ECM)‐based scaffolds through the process called ‘decellularization’ and proved to show the potential of recellularization with selected cell populations, particularly with stem cells. In fact, decellularized stem cell matrix (DSCM) has also emerged as a potent biological scaffold for controlling stem cell fate and function during tissue organization. Despite the proven potential of decellularized scaffolds in tissue engineering, the molecular mechanism responsible for stem cell interactions with decellularized scaffolds is still unclear. Stem cells interact with, and respond to, various signals/cues emanating from their ECM. The ability to harness the regenerative potential of stem cells via decellularized ECM‐based scaffolds has promising implications for tissue‐regenerative medicine. Keeping these points in view, this article reviews the current status of decellularized scaffolds for stem cells, with particular focus on: (a) concept and various methods of decellularization; (b) interaction of stem cells with decellularized scaffolds; (c) current recellularization strategies, with associated challenges; and (iv) applications of the decellularized scaffolds in stem cell‐driven tissue engineering and regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd.

[1]  Alexander Lembcke,et al.  Hemodynamic characteristics of the Matrix P decellularized xenograft for pulmonary valve replacement during the Ross operation. , 2005, The Journal of heart valve disease.

[2]  Buddy D Ratner,et al.  Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. , 2011, Tissue engineering. Part C, Methods.

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

[4]  S. Grant,et al.  Method of preparing a decellularized porcine tendon using tributyl phosphate. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[5]  G. An,et al.  Engineering of corpus cavernosum using vascular endothelial growth factor-expressing muscle-derived stem cells seeded on acellular corporal collagen matrices. , 2013, Urology.

[6]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[7]  L. Flynn,et al.  The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. , 2010, Biomaterials.

[8]  P. Macchiarini,et al.  Both epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs. , 2010, The Journal of thoracic and cardiovascular surgery.

[9]  D J Mooney,et al.  Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system. , 2000, Tissue engineering.

[10]  M. Pei,et al.  Antioxidation of decellularized stem cell matrix promotes human synovium-derived stem cell-based chondrogenesis. , 2013, Stem cells and development.

[11]  John Fisher,et al.  Development and characterisation of a full-thickness acellular porcine bladder matrix for tissue engineering. , 2007, Biomaterials.

[12]  J. G. Roderjan,et al.  Decellularized heterografts versus cryopreserved homografts: experimental study in sheep model. , 2009, Revista brasileira de cirurgia cardiovascular : orgao oficial da Sociedade Brasileira de Cirurgia Cardiovascular.

[13]  Donald W. Fink.  FDA Regulation of Stem Cell–Based Products , 2009, Science.

[14]  R. Holubkov,et al.  Clinical performance of decellularized cryopreserved valved allografts compared with standard allografts in the right ventricular outflow tract. , 2010, The Annals of thoracic surgery.

[15]  S. Felisbino,et al.  Light-emitting diode effects on combined decellularization of tracheae. A novel approach to obtain biological scaffolds. , 2014, Acta cirurgica brasileira.

[16]  D. Prockop,et al.  Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats--similarities to astrocyte grafts. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[17]  D. Drez,et al.  Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts , 1991, The American journal of sports medicine.

[18]  Anthony Atala,et al.  Tissue-engineered autologous vaginal organs in patients: a pilot cohort study , 2014, The Lancet.

[19]  P. Lelkes,et al.  Enhanced reseeding of decellularized rodent lungs with mouse embryonic stem cells. , 2014, Biomaterials.

[20]  Soichiro Kitamura,et al.  Cell removal with supercritical carbon dioxide for acellular artificial tissue , 2008 .

[21]  A. Emili,et al.  Tissue subcellular fractionation and protein extraction for use in mass-spectrometry-based proteomics , 2006, Nature Protocols.

[22]  Xiujuan Wu,et al.  Method for perfusion decellularization of porcine whole liver and kidney for use as a scaffold for clinical‐scale bioengineering engrafts , 2015, Xenotransplantation.

[23]  V. Shanmuganathan,et al.  Optimization of amniotic membrane (AM) denuding for tissue engineering. , 2008, Tissue engineering. Part C, Methods.

[24]  Boris Rubinsky,et al.  Nonthermal irreversible electroporation for tissue decellularization. , 2010, Journal of biomechanical engineering.

[25]  Jian Wei Xu,et al.  Conditions affecting cell seeding onto three-dimensional scaffolds for cellular-based biodegradable implants. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[26]  T. Fujisato,et al.  Reconstruction of small diameter arteries using decellularized vascular scaffolds. , 2014, Journal of medical and dental sciences.

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

[28]  L. Niklason,et al.  Novel utilization of serum in tissue decellularization. , 2010, Tissue engineering. Part C, Methods.

[29]  M. Domingues,et al.  Morphofunctional characterization of decellularized vena cava as tissue engineering scaffolds. , 2014, Experimental cell research.

[30]  W. Konertz,et al.  Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure. , 2007, The Annals of thoracic surgery.

[31]  Stephen F Badylak,et al.  RETRACTED: Engineered whole organs and complex tissues , 2012, The Lancet.

[32]  O. Lee,et al.  Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering. , 2014, Biomaterials.

[33]  J. Ball,et al.  Porcine small intestine submucosa matrix (Surgisis) for esophageal perforation. , 2011, The Annals of thoracic surgery.

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

[35]  Yimin Zhao,et al.  Clinical transplantation of a tissue-engineered airway , 2009, The Lancet.

[36]  P. Vogt,et al.  Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft. , 2010, Bone.

[37]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[38]  Artur Lichtenberg,et al.  Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells , 2006, Circulation.

[39]  Thomas W Gilbert,et al.  Strategies for tissue and organ decellularization , 2012, Journal of cellular biochemistry.

[40]  A. Kajbafzadeh,et al.  Determining the optimal decellularization and sterilization protocol for preparing a tissue scaffold of a human-sized liver tissue. , 2013, Tissue engineering. Part C, Methods.

[41]  Jerry C. Hu,et al.  Advances in tissue engineering through stem cell‐based co‐culture , 2015, Journal of tissue engineering and regenerative medicine.

[42]  Claire Crowley,et al.  Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study , 2012, The Lancet.

[43]  J. Andersen,et al.  Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction , 2011, PloS one.

[44]  Jiawei Shi,et al.  Tissue engineering of heart valves: PEGylation of decellularized porcine aortic valve as a scaffold for in vitro recellularization , 2013, BioMedical Engineering OnLine.

[45]  S. Moran,et al.  Early Clinical Outcomes with the Use of Decellularized Nerve Allograft for Repair of Sensory Defects Within the Hand , 2009, Hand.

[46]  Seeram Ramakrishna,et al.  Biomaterials: A Nano Approach , 2010 .

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

[48]  Pedro M. Baptista,et al.  Liver Regeneration and Bioengineering - The Emergence of Whole Organ Scaffolds , 2012 .

[49]  A. Dhawan,et al.  Human hepatocyte transplantation: state of the art , 2009, Journal of internal medicine.

[50]  D. Zurakowski,et al.  Prenatal tracheal reconstruction with a hybrid amniotic mesenchymal stem cells-engineered construct derived from decellularized airway. , 2012, Journal of pediatric surgery.

[51]  G. Gerosa,et al.  The influence of heart valve leaflet matrix characteristics on the interaction between human mesenchymal stem cells and decellularized scaffolds. , 2009, Biomaterials.

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

[53]  J. Lawson,et al.  Multicenter evaluation of the bovine mesenteric vein bioprostheses for hemodialysis access in patients with an earlier failed prosthetic graft. , 2005, Journal of the American College of Surgeons.

[54]  Sangeeta N Bhatia,et al.  Assessing porcine liver-derived biomatrix for hepatic tissue engineering. , 2004, Tissue engineering.

[55]  Lucas R. Smith,et al.  Method for decellularizing skeletal muscle without detergents or proteolytic enzymes. , 2011, Tissue engineering. Part C, Methods.

[56]  T. Ma,et al.  Extracellular matrices decellularized from embryonic stem cells maintained their structure and signaling specificity. , 2014, Tissue engineering. Part A.

[57]  M. Pei,et al.  Reconstruction of an in vitro tissue-specific microenvironment to rejuvenate synovium-derived stem cells for cartilage tissue engineering. , 2009, Tissue engineering. Part A.

[58]  Christopher K Breuer,et al.  Development of decellularized human umbilical arteries as small-diameter vascular grafts. , 2009, Tissue engineering. Part A.

[59]  Stephen F Badylak,et al.  Antibacterial activity within degradation products of biological scaffolds composed of extracellular matrix. , 2006, Tissue engineering.

[60]  Seok-Ho Hong,et al.  Sterilization using Electrolyzed Water Highly Retains the Biological Properties in Tissue-Engineered Porcine Liver Scaffold , 2013, The International journal of artificial organs.

[61]  Wendell Q. Sun,et al.  Calorimetric study of extracellular tissue matrix degradation and instability after gamma irradiation. , 2008, Acta biomaterialia.

[62]  K J Halbhuber,et al.  Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves. , 2003, Journal of structural biology.

[63]  Andrew L. Weinstein,et al.  Development of an acellular bioengineered matrix with a dominant vascular pedicle. , 2010, The Journal of surgical research.

[64]  Daniel I. C. Wang,et al.  Effects of paddle impeller geometry on power input and mass transfer in small‐scale animal cell culture vessels , 1989, Biotechnology and bioengineering.

[65]  Jiwang Zhang,et al.  Stem Cell Niche: Microenvironment and Beyond* , 2008, Journal of Biological Chemistry.

[66]  Vikas Prabhakar,et al.  Decellularized native and engineered arterial scaffolds for transplantation. , 2003, Cell transplantation.

[67]  Paolo De Coppi,et al.  Tissue engineered human tracheas for in vivo implantation. , 2010, Biomaterials.

[68]  Min Yang,et al.  Favorable effects of the detergent and enzyme extraction method for preparing decellularized bovine pericardium scaffold for tissue engineered heart valves. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[69]  Stephen F Badylak,et al.  Decellularization of tissues and organs. , 2006, Biomaterials.

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

[71]  P. Macchiarini,et al.  Dynamic decellularization and cross-linking of rat tracheal matrix. , 2014, Biomaterials.

[72]  Xi Ren,et al.  Perfusion decellularization of whole organs , 2014, Nature Protocols.

[73]  Stephen F Badylak,et al.  The basement membrane component of biologic scaffolds derived from extracellular matrix. , 2006, Tissue engineering.

[74]  Stephen F Badylak,et al.  Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. , 2007, Tissue engineering.

[75]  Qijin Lu,et al.  Novel porous aortic elastin and collagen scaffolds for tissue engineering. , 2004, Biomaterials.

[76]  C. Stamm,et al.  Preparation of cardiac extracellular matrix scaffolds by decellularization of human myocardium. , 2013, Journal of biomedical materials research. Part A.

[77]  Ann E Rundell,et al.  Biaxial strength of multilaminated extracellular matrix scaffolds. , 2004, Biomaterials.

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

[79]  S. Badylak,et al.  Uniaxial and biaxial properties of terminally sterilized porcine urinary bladder matrix scaffolds. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[80]  Philipp Jungebluth,et al.  The first tissue-engineered airway transplantation: 5-year follow-up results , 2014, The Lancet.

[81]  Jean A. Niles,et al.  Production and assessment of decellularized pig and human lung scaffolds. , 2013, Tissue engineering. Part A.

[82]  Jie Gong,et al.  Effects of extracellular matrix and neighboring cells on induction of human embryonic stem cells into retinal or retinal pigment epithelial progenitors. , 2008, Experimental eye research.

[83]  James Chang,et al.  Human Flexor Tendon Tissue Engineering: In Vivo Effects of Stem Cell Reseeding , 2013, Plastic and reconstructive surgery.

[84]  Charles L. Rodriguez-Feo,et al.  Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts. , 2015, The Journal of surgical research.

[85]  Benjamin C. Weed,et al.  Decellularized Scaffolds: Concepts, Methodologies, and Applications in Cardiac Tissue Engineering and Whole-Organ Regeneration , 2014 .

[86]  P. Macchiarini,et al.  Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering. , 2014, Biomaterials.

[87]  Artur Lichtenberg,et al.  Use of Fresh Decellularized Allografts for Pulmonary Valve Replacement May Reduce the Reoperation Rate in Children and Young Adults: Early Report , 2011, Circulation.

[88]  Angela Panoskaltsis-Mortari,et al.  Automated decellularization of intact, human-sized lungs for tissue engineering. , 2015, Tissue engineering. Part C, Methods.

[89]  P. McFetridge,et al.  Preparation of ex vivo-based biomaterials using convective flow decellularization. , 2009, Tissue engineering. Part C, Methods.

[90]  A. Rajan,et al.  Biomaterial properties of cholecyst-derived scaffold recovered by a non-detergent/enzymatic method. , 2014, Journal of biomedical materials research. Part B, Applied biomaterials.

[91]  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.

[92]  W M Miller,et al.  Optimization and Critical Evaluation of Decellularization Strategies to Develop Renal Extracellular Matrix Scaffolds as Biological Templates for Organ Engineering and Transplantation , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

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

[94]  Kerry A. Daly,et al.  Effect of the alphaGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. , 2009, Tissue engineering. Part A.

[95]  Torsten Seemann,et al.  Pseudomonas aeruginosa AES-1 Exhibits Increased Virulence Gene Expression during Chronic Infection of Cystic Fibrosis Lung , 2011, PloS one.

[96]  S. E. James,et al.  A review of tissue-engineered skin bioconstructs available for skin reconstruction , 2010, Journal of The Royal Society Interface.

[97]  Chih-Hsun Lin,et al.  Evaluation of Decellularized Extracellular Matrix of Skeletal Muscle for Tissue Engineering , 2014, The International journal of artificial organs.

[98]  Lujie Song,et al.  Reconstruction of penile urethra with the 3-dimensional porous bladder acellular matrix in a rabbit model. , 2014, Urology.

[99]  A. K. Gulati,et al.  Evaluation of acellular and cellular nerve grafts in repair of rat peripheral nerve. , 1988, Journal of neurosurgery.

[100]  J. Leor,et al.  Cells, scaffolds, and molecules for myocardial tissue engineering. , 2005, Pharmacology & therapeutics.

[101]  Shih-Han Hung,et al.  Larynx decellularization: combining freeze-drying and sonication as an effective method. , 2013, Journal of voice : official journal of the Voice Foundation.

[102]  X. Ye,et al.  Development of decellularized aortic valvular conduit coated by heparin-SDF-1α multilayer. , 2015, The Annals of thoracic surgery.

[103]  R. Chan,et al.  A biodegradable, acellular xenogeneic scaffold for regeneration of the vocal fold lamina propria. , 2006, Tissue engineering.

[104]  Ning Zhang,et al.  The differentiation of MSCs into functional hepatocyte-like cells in a liver biomatrix scaffold and their transplantation into liver-fibrotic mice. , 2012, Biomaterials.

[105]  Christine E Schmidt,et al.  Engineering an improved acellular nerve graft via optimized chemical processing. , 2004, Tissue engineering.

[106]  Lanjuan Li,et al.  Stem cells with decellularized liver scaffolds in liver regeneration and their potential clinical applications , 2015, Liver international : official journal of the International Association for the Study of the Liver.

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

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

[109]  Almudena Martinez-Fernandez,et al.  Embryonic Decellularized Cardiac Scaffold Supports Embryonic Stem Cell Differentiation to Produce Beating Cardiac Tissue , 2014 .

[110]  M. Bissell,et al.  Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression? , 1987, Progress in clinical and biological research.

[111]  S. Badylak,et al.  Porcine small intestinal submucosa as a dural substitute. , 1999, Surgical neurology.

[112]  Sara Mantero,et al.  Clinical transplantation of a tissue-engineered airway , 2008, The Lancet.

[113]  B. Murphy,et al.  The application of a thermoresponsive chitosan/β-GP gel to enhance cell repopulation of decellularized vascular scaffolds. , 2014, Journal of biomedical materials research. Part B, Applied biomaterials.

[114]  S. Badylak,et al.  The use of xenogeneic small intestinal submucosa as a biomaterial for Achilles tendon repair in a dog model. , 1995, Journal of biomedical materials research.

[115]  Gordana Vunjak-Novakovic,et al.  Engineering bone tissue substitutes from human induced pluripotent stem cells , 2013, Proceedings of the National Academy of Sciences.

[116]  X. Sui,et al.  In vivo cartilage repair using adipose‐derived stem cell‐loaded decellularized cartilage ECM scaffolds , 2014, Journal of tissue engineering and regenerative medicine.

[117]  H. Ejnell,et al.  Replacement of a tracheal stenosis with a tissue-engineered human trachea using autologous stem cells: a case report. , 2014, Tissue engineering. Part A.

[118]  F. Mouquet,et al.  In vivo autologous recellularization of a tissue-engineered heart valve: are bone marrow mesenchymal stem cells the best candidates? , 2007, The Journal of thoracic and cardiovascular surgery.

[119]  Warren L. Grayson,et al.  Engineering bone tissue from human embryonic stem cells , 2012, Proceedings of the National Academy of Sciences.

[120]  Matthew J. Robertson,et al.  Optimizing Recellularization of Whole Decellularized Heart Extracellular Matrix , 2014, PloS one.

[121]  Masato Tanaka,et al.  The use of sonication treatment to completely decellularize blood arteries: A pilot study , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[122]  G. Vunjak‐Novakovic,et al.  Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. , 2010, Tissue engineering. Part A.

[123]  M Pei,et al.  A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering. , 2011, European cells & materials.

[124]  Zhiliang Gao,et al.  Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular Matrix , 2013, BioMed research international.

[125]  A. Jones,et al.  Decellularization of human dermis using non-denaturing anionic detergent and endonuclease: a review , 2014, Cell and Tissue Banking.