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

Joan Nichols, Saverio La Francesca, Jean A. Niles, Stephanie P. Vega, Lissenya B. Argueta, Luba Frank, David C. Christiani, Richard Pyles, Blanca E. Himes, Ruyang Zhang, Su Li, Jason Sakamoto, Jessica Rhudy, Greg Hendricks, Filippo Begarani, Xuewu Liu, Igor Patrikeev, Rahul Pal, Emiliya Usheva, Gracie VargasAaron Miller, Lee Woodson, Adam Wacher, Maria Grimaldo, Daniil Weaver, Ron Mlcak, Joaquin Cortiella

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaao3926
JournalScience Translational Medicine
Volume10
Issue number452
DOIs
StatePublished - Aug 1 2018

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Lung Transplantation
Animal Models
Lung
Transplants
Tissue Survival
Graft Rejection
Microvessels
Blood Vessels
Intercellular Signaling Peptides and Proteins
Pneumonectomy
Microbiota
Autografts
Bioreactors
Organ Transplantation
Tissue Engineering
Cardiovascular System
Respiratory System
Pulmonary Artery
Swine
Gases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Production and transplantation of bioengineered lung into a large-animal model. / Nichols, Joan; La Francesca, Saverio; Niles, Jean A.; Vega, Stephanie P.; Argueta, Lissenya B.; Frank, Luba; Christiani, David C.; Pyles, Richard; Himes, Blanca E.; Zhang, Ruyang; Li, Su; Sakamoto, Jason; Rhudy, Jessica; Hendricks, Greg; Begarani, Filippo; Liu, Xuewu; Patrikeev, Igor; Pal, Rahul; Usheva, Emiliya; Vargas, Gracie; Miller, Aaron; Woodson, Lee; Wacher, Adam; Grimaldo, Maria; Weaver, Daniil; Mlcak, Ron; Cortiella, Joaquin.

In: Science Translational Medicine, Vol. 10, No. 452, eaao3926, 01.08.2018.

Research output: Contribution to journalArticle

Nichols, J, La Francesca, S, Niles, JA, Vega, SP, Argueta, LB, Frank, L, Christiani, DC, Pyles, R, 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, Wacher, A, Grimaldo, M, Weaver, D, Mlcak, R & Cortiella, J 2018, 'Production and transplantation of bioengineered lung into a large-animal model', Science Translational Medicine, vol. 10, no. 452, eaao3926. https://doi.org/10.1126/scitranslmed.aao3926
Nichols, Joan ; La Francesca, Saverio ; Niles, Jean A. ; Vega, Stephanie P. ; Argueta, Lissenya B. ; Frank, Luba ; Christiani, David C. ; Pyles, Richard ; Himes, Blanca E. ; Zhang, Ruyang ; Li, Su ; Sakamoto, Jason ; Rhudy, Jessica ; Hendricks, Greg ; Begarani, Filippo ; Liu, Xuewu ; Patrikeev, Igor ; Pal, Rahul ; Usheva, Emiliya ; Vargas, Gracie ; Miller, Aaron ; Woodson, Lee ; Wacher, Adam ; Grimaldo, Maria ; Weaver, Daniil ; Mlcak, Ron ; Cortiella, Joaquin. / Production and transplantation of bioengineered lung into a large-animal model. In: Science Translational Medicine. 2018 ; Vol. 10, No. 452.
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