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Nat Biotechnol. 2015 Oct;33(10):1097-102. doi: 10.1038/nbt.3354. Epub 2015 Sep 14.

Engineering pulmonary vasculature in decellularized rat and human lungs.

Ren X1,2, Moser PT1,2, Gilpin SE1,2, Okamoto T1,2, Wu T1,2, Tapias LF1,2,3, Mercier FE1,2, Xiong L1,2, Ghawi R1,2,4, Scadden DT1,2,5, Mathisen DJ2,3, Ott HC1,2,3,5.

Author information

1
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
2
Harvard Medical School, Boston, Massachusetts, USA.
3
Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.
4
Harvard College, Cambridge, Massachusetts, USA.
5
Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.

Abstract

Bioengineered lungs produced from patient-derived cells may one day provide an alternative to donor lungs for transplantation therapy. Here we report the regeneration of functional pulmonary vasculature by repopulating the vascular compartment of decellularized rat and human lung scaffolds with human cells, including endothelial and perivascular cells derived from induced pluripotent stem cells. We describe improved methods for delivering cells into the lung scaffold and for maturing newly formed endothelium through co-seeding of endothelial and perivascular cells and a two-phase culture protocol. Using these methods we achieved ∼75% endothelial coverage in the rat lung scaffold relative to that of native lung. The regenerated endothelium showed reduced vascular resistance and improved barrier function over the course of in vitro culture and remained patent for 3 days after orthotopic transplantation in rats. Finally, we scaled our approach to the human lung lobe and achieved efficient cell delivery, maintenance of cell viability and establishment of perfusable vascular lumens.

PMID:
26368048
DOI:
10.1038/nbt.3354
[Indexed for MEDLINE]

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