Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 10, Pages 4669-4674Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911465107
Keywords
bone marrow; monocyte chemoattractant protein-1; tissue engineering; neovascularization
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Funding
- Gunze
- National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR46032]
- National Institutes of Health [KO8-HL083980, PO1-HL070295, R01-GM072194, R01-L085416]
- T32-predoctoral research fellowship
- American Medical Association Foundation
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Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.
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