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

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.

journal_name

Sci Transl Med

authors

Nichols JE,La Francesca S,Niles JA,Vega SP,Argueta LB,Frank L,Christiani DC,Pyles RB,Himes BE,Zhang R,Li S,Sakamoto J,Rhudy J,Hendricks G,Begarani F,Liu X,Patrikeev I,Pal R,Usheva E,Vargas G,Miller A,Woodson L,

doi

10.1126/scitranslmed.aao3926

subject

Has Abstract

pub_date

2018-08-01 00:00:00

issue

452

eissn

1946-6234

issn

1946-6242

pii

10/452/eaao3926

journal_volume

10

pub_type

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