Research ArticleTissue Engineering

Production and transplantation of bioengineered lung into a large-animal model

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Science Translational Medicine  01 Aug 2018:
Vol. 10, Issue 452, eaao3926
DOI: 10.1126/scitranslmed.aao3926

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New life for lungs

Lungs are complex organs to engineer: They contain multiple specialized cell types in extracellular matrix with a unique architecture that must maintain compliance during respiration. Nichols et al. tackled the challenges of vascular perfusion, recellularization, and engraftment of tissue-engineered lungs in a clinically relevant pig model. Nanoparticle and hydrogel delivery of growth factors promoted cell adhesion to whole decellularized pig lung scaffolds. Autologous cell–seeded bioengineered lungs showed vascular perfusion via collateral circulation within 2 weeks after transplantation. The transplanted bioengineered lungs became aerated and developed native lung-like microbiomes. One pig had no respiratory symptoms when euthanized a full 2 months after transplant. This work represents a considerable advance in the lung tissue engineering field and brings tissue-engineered lungs closer to the realm of clinical possibility.

Abstract

The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which requires systemic circulation to support tissue survival and coordination of circulatory and respiratory systems to ensure proper gas exchange. To advance our understanding of vascularization after bioengineered organ transplantation, we produced and transplanted BEL without creation of a pulmonary artery anastomosis in a porcine model. A single pneumonectomy, performed 1 month before BEL implantation, provided the source of autologous cells used to bioengineer the organ on an acellular lung scaffold. During 30 days of bioreactor culture, we facilitated systemic vessel development using growth factor–loaded microparticles. We evaluated recipient survival, autograft (BEL) vascular and parenchymal tissue development, graft rejection, and microbiome reestablishment in autografted animals 10 hours, 2 weeks, 1 month, and 2 months after transplant. BEL became well vascularized as early as 2 weeks after transplant, and formation of alveolar tissue was observed in all animals (n = 4). There was no indication of transplant rejection. BEL continued to develop after transplant and did not require addition of exogenous growth factors to drive cell proliferation or lung and vascular tissue development. The sterile BEL was seeded and colonized by the bacterial community of the native lung.

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