Haiyang Zhou1,2,3, Kentaro Kitano1,2, Xi Ren1,2, Taufiek Konrad Rajab1,2, Min Wu1,2, Sarah E Gilpin1,2, Tong Wu1,2, Lauren Baugh4, Lauren D Black4, Douglas J Mathisen2,5, Harald C Ott1,2,5,6. 1. Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA. 2. Harvard Medical School, Boston, MA. 3. Department of Surgery, Changzheng Hospital, Shanghai, China. 4. Department of Biomedical Engineering, Tufts University, Medford, MA. 5. Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA. 6. Harvard Stem Cell Institute, Boston, MA.
Abstract
OBJECTIVE: Bioengineering of viable, functional, and implantable human lung grafts on porcine matrix. SUMMARY BACKGROUND DATA: Implantable bioartificial organ grafts could revolutionize transplant surgery. To date, several milestones toward that goal have been achieved in rodent models. To make bioengineered organ grafts clinically relevant, scaling to human cells and graft size are the next steps. METHODS: We seeded porcine decellularized lung scaffolds with human airway epithelial progenitor cells derived from rejected donor lungs, and banked human umbilical vein endothelial cells. We subsequently enabled tissue formation in whole organ culture. The resulting grafts were then either analyzed in vitro (n = 15) or transplanted into porcine recipients in vivo (n = 3). RESULTS: By repopulating porcine extracellular matrix scaffolds with human endothelial cells, we generated pulmonary vasculature with mature endothelial lining and sufficient anti-thrombotic function to enable blood perfusion. By repopulating the epithelial surface with human epithelial progenitor cells, we created a living, functioning gas exchange graft. After surgical implantation, the bioengineered lung grafts were able to withstand physiological blood flow from the recipient's pulmonary circulation, and exchanged gases upon ventilation during the 1-hour observation. CONCLUSIONS: Engineering and transplantation of viable lung grafts based on decellularized porcine lung scaffolds and human endothelial and epithelial cells is technically feasible. Further graft maturation will be necessary to enable higher-level functions such as mucociliary clearance, and ventilation-perfusion matching.
OBJECTIVE: Bioengineering of viable, functional, and implantable human lung grafts on porcine matrix. SUMMARY BACKGROUND DATA: Implantable bioartificial organ grafts could revolutionize transplant surgery. To date, several milestones toward that goal have been achieved in rodent models. To make bioengineered organ grafts clinically relevant, scaling to human cells and graft size are the next steps. METHODS: We seeded porcine decellularized lung scaffolds with human airway epithelial progenitor cells derived from rejected donor lungs, and banked human umbilical vein endothelial cells. We subsequently enabled tissue formation in whole organ culture. The resulting grafts were then either analyzed in vitro (n = 15) or transplanted into porcine recipients in vivo (n = 3). RESULTS: By repopulating porcine extracellular matrix scaffolds with human endothelial cells, we generated pulmonary vasculature with mature endothelial lining and sufficient anti-thrombotic function to enable blood perfusion. By repopulating the epithelial surface with human epithelial progenitor cells, we created a living, functioning gas exchange graft. After surgical implantation, the bioengineered lung grafts were able to withstand physiological blood flow from the recipient's pulmonary circulation, and exchanged gases upon ventilation during the 1-hour observation. CONCLUSIONS: Engineering and transplantation of viable lung grafts based on decellularized porcine lung scaffolds and human endothelial and epithelial cells is technically feasible. Further graft maturation will be necessary to enable higher-level functions such as mucociliary clearance, and ventilation-perfusion matching.
Authors: Jason K D Chan; Eric A Chadwick; Daisuke Taniguchi; Mohammadali Ahmadipour; Takaya Suzuki; David Romero; Cristina Amon; Thomas K Waddell; Golnaz Karoubi; Aimy Bazylak Journal: Front Bioeng Biotechnol Date: 2022-04-27
Authors: Juan J Uriarte; Franziska E Uhl; Sara E Rolandsson Enes; Robert A Pouliot; Daniel J Weiss Journal: Curr Opin Organ Transplant Date: 2018-12 Impact factor: 2.640
Authors: Mattia Francesco Maria Gerli; Jacques Paul Guyette; Daniele Evangelista-Leite; Brian Burns Ghoshhajra; Harald Christian Ott Journal: PLoS One Date: 2018-01-19 Impact factor: 3.240