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Engineering pulmonary vasculature in decellularized rat and human lungs.
- Source :
-
Nature biotechnology [Nat Biotechnol] 2015 Oct; Vol. 33 (10), pp. 1097-102. Date of Electronic Publication: 2015 Sep 14. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Cell-Free System
Cells, Cultured
Endothelial Cells cytology
Equipment Design
Equipment Failure Analysis
Humans
Male
Neovascularization, Physiologic physiology
Rats
Rats, Sprague-Dawley
Regeneration physiology
Species Specificity
Endothelial Cells physiology
Lung chemistry
Pulmonary Artery cytology
Pulmonary Artery growth & development
Tissue Engineering instrumentation
Tissue Scaffolds
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1696
- Volume :
- 33
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Nature biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 26368048
- Full Text :
- https://doi.org/10.1038/nbt.3354