Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling

Jason D. Roha, Rajendra Sawh-Martinez, Matthew P. Brennan, Steven M. Jay, Lesley Devine, Deepak A. Rao, Tai Yi, Tamar L. Mirensky, Ani Nalbandian, Brooks Udelsman, Narutoshi Hibino, Toshiharu Shinoka, W. Mark Saltzman, Edward Snyder, Themis R. Kyriakides, Jordan S. Pober, Christopher K. Breuer

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4669-4674
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number10
DOIs
StatePublished - Mar 9 2010
Externally publishedYes

Keywords

  • Bone marrow
  • Monocyte chemoattractant protein-1
  • Neovascularization
  • Tissue engineering

ASJC Scopus subject areas

  • General

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