Production and transplantation of bioengineered lung into a large-animal model
| Autor: | Igor Patrikeev, Aaron L. Miller, Joan E. Nichols, Emiliya Usheva, Greg Hendricks, Daniil Weaver, Richard B. Pyles, Joaquin Cortiella, Lissenya B. Argueta, Rahul Pal, Saverio La Francesca, Blanca E. Himes, Luba Frank, Jean A. Niles, Jason Sakamoto, Lee C. Woodson, Filippo Begarani, Su Li, Ruyang Zhang, Adam Wacher, Ron Mlcak, Stephanie P. Vega, Jessica Rhudy, David C. Christiani, Xuewu Liu, Grace Vargas, Maria Grimaldo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pathology Swine medicine.medical_treatment Biomedical Engineering Organ transplantation 03 medical and health sciences Pneumonectomy 0302 clinical medicine Tissue engineering Parenchyma Animals Medicine Lung transplantation Lymphangiogenesis Lung Tissue Scaffolds business.industry Microbiota Immunity General Medicine medicine.disease Transplant rejection Transplantation 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030228 respiratory system Models Animal Transcriptome business Lung Transplantation |
| Zdroj: | Science Translational Medicine. 10 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aao3926 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|