Can stem cells be used to generate new lungs? Ex vivo lung bioengineering with decellularized whole lung scaffolds
Darcy E. Wagner,Ryan W. Bonvillain,Todd Jensen,Eric D. Girard,Bruce A. Bunnell,Christine Finck,Andrew M. Hoffman,Daniel J. Weiss +7 more
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TLDR
A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds and Ideally, patient‐derived autologous cells would be used for lung Recellularization as they have the potential to reduce the need for post‐transplant immunosuppression.Abstract:
For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells towards the goal of regenerating functional tissues. Several decellularization strategies have been employed for lungs; however, there is no consensus on the optimal approach. A variety of cell types have been investigated as potential candidates for effective recellularization of acellular lung scaffolds. Candidate cells that might be best utilized are those which can be easily and reproducibly isolated, expanded in vitro, seeded onto decellularized matrices, induced to differentiate into pulmonary lineage cells, and which survive to functional maturity. Whole lung cell suspensions, endogenous progenitor cells, embryonic and adult stem cells and induced pluripotent stem (iPS) cells have been investigated for their applicability to repopulate acellular lung matrices. Ideally, patient-derived autologous cells would be used for lung recellularization as they have the potential to reduce the need for post-transplant immunosuppression. Several studies have performed transplantation of rudimentary bioengineered lung scaffolds in animal models with limited, short-term functionality but much further study is needed.read more
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The instructive extracellular matrix of the lung: basic composition and alterations in chronic lung disease.
Gerald Burgstaller,Bettina Oehrle,Michael Gerckens,Eric S. White,Herbert B. Schiller,Oliver Eickelberg +5 more
TL;DR: This review summarises the available data about the structure and function of the pulmonary ECM, and highlights changes that occur in idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and lung cancer.
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The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future.
Maria C. Basil,Jeremy Katzen,Anna Engler,Minzhe Guo,Michael J. Herriges,Jaymin J. Kathiriya,Rebecca Windmueller,Alexandra B. Ysasi,William J. Zacharias,H.A. Chapman,Darrell N. Kotton,Jason R. Rock,Hans-Willem Snoeck,Gordana Vunjak-Novakovic,Jeffrey A. Whitsett,Edward E. Morrisey +15 more
TL;DR: Key aspects of lung repair and regeneration are discussed, including the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung Repair and regeneration.
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Extracellular matrix in lung development, homeostasis and disease
Yong Zhou,Jeffrey C. Horowitz,Alexandra Naba,Namasivayam Ambalavanan,Kamran Atabai,Jenna L. Balestrini,Peter B. Bitterman,Richard A. Corley,Bi-Sen Ding,Adam J. Engler,Kirk C. Hansen,James S. Hagood,Farrah Kheradmand,Qing S. Lin,Enid Neptune,Laura E. Niklason,Luis A. Ortiz,William C. Parks,Daniel J. Tschumperlin,Eric S. White,Harold A. Chapman,Victor J. Thannickal +21 more
TL;DR: This review assesses the current state of lung ECM biology, including fundamental advances in ECM composition, dynamics, topography, and biomechanics; the role of the ECM in normal and aberrant lung development, adult lung diseases and autoimmunity; andECM in the regulation of the stem cell niche.
Journal ArticleDOI
A Review of Cellularization Strategies for Tissue Engineering of Whole Organs
TL;DR: The cell types, delivery methods, and bioreactors employed for recellularization are discussed along with commercial and clinical considerations, such as immunogenicity, biocompatibility, and Food and Drug Administartion regulation.
Journal ArticleDOI
A Nonhuman Primate Model of Lung Regeneration: Detergent-Mediated Decellularization and Initial In Vitro Recellularization with Mesenchymal Stem Cells
Ryan W. Bonvillain,Svitlana Danchuk,Deborah E. Sullivan,Aline M. Betancourt,Julie A. Semon,Michelle E. Eagle,Jacques P. Mayeux,Ashley N. Gregory,Guangdi Wang,Ian K. Townley,Zachary D. Borg,Daniel J. Weiss,Bruce A. Bunnell +12 more
TL;DR: Nonhuman primates (NHP) provide a highly relevant preclinical model with which to assess the feasibility of recellularized lung scaffolds for human lung transplantation and both bone marrow- and adipose-derived mesenchymal stem cells attach to the decellularized lung matrix and can be maintained within this environment in vitro, suggesting that these cells may be promising candidates and useful tools for lung regeneration.
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