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Ann Surg. 2018 Mar;267(3):590-598. doi: 10.1097/SLA.0000000000002129.

Bioengineering Human Lung Grafts on Porcine Matrix.

Zhou H1,2,3, Kitano K1,2, Ren X1,2, Rajab TK1,2, Wu M1,2, Gilpin SE1,2, Wu T1,2, Baugh L4, Black LD4, Mathisen DJ2,5, Ott HC1,2,5,6.

Author information

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.

PMID:
28085694
DOI:
10.1097/SLA.0000000000002129
[Indexed for MEDLINE]

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