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Sci Transl Med. 2018 Aug 1;10(452). pii: eaao3926. doi: 10.1126/scitranslmed.aao3926.

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

Author information

1
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA. jnichols@utmb.edu jocortie@utmb.edu.
2
Biostage Inc., Holliston, MA 01746, USA.
3
Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
4
Department of Microbiology and Immunology, UTMB, Galveston, TX 77555, USA.
5
Weill Cornell Medical College, New York, NY 10065, USA.
6
Department of Radiology, UTMB, Galveston, TX 77555, USA.
7
Pulmonary Division, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
8
Environmental, Occupational Medicine, Epidemiology Department, TH Chan School of Public Health, Harvard University, Boston, MA 02115, USA.
9
Galveston National Laboratory, Assay Development Core, UTMB, Galveston, TX 77555, USA.
10
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
11
Houston Methodist Hospital Research Institute, Houston, TX 77030, USA.
12
Radiology Division of Cell Biology, University of Massachusetts Medical School, Worchester, MA 01605, USA.
13
Center for Biomedical Engineering, UTMB, Galveston, TX 77555, USA.
14
University of Texas Southwestern Medical School, Dallas, TX 75390, USA.
15
Department of Anesthesiology, UTMB, Galveston, TX 77555, USA.
16
Shriners Hospital for Children, Galveston, TX 77550, USA.
17
Department of Anesthesiology, UTMB, Galveston, TX 77555, USA. jnichols@utmb.edu jocortie@utmb.edu.

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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