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Cardiovascular Research 2007 75(3):618-628; doi:10.1016/j.cardiores.2007.04.018
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Copyright © 2007, European Society of Cardiology

Functional tissue-engineered blood vessels from bone marrow progenitor cells

Jin Yu Liua, Daniel D. Swartzb, Hao Fan Penga, Sylvia F. Guginoc, James A. Russellc and Stelios T. Andreadisa,*

aBioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260, United States
bWomen and Children's Hospital of Buffalo, University at Buffalo, The State University of New York, Buffalo, NY, United States
cDepartment of Physiology and Biophysics, University at Buffalo, The State University of New York, Buffalo, NY, United States

* Corresponding author. Tel.: +1 716 645 2911x2204; fax: +1 716 645 3822. sandread{at}eng.buffalo.edu

Objective Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration.

Methods We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting.

Results As compared to vascular SMC, bone marrow-derived smooth muscle progenitor cells (BM-SMPC) exhibited similar morphology, showed higher proliferation potential and expressed several SMC markers including {alpha}-actin, calponin, myosin heavy chain, smoothelin, caldesmon and SM22. When embedded in fibrin hydrogels, BM-SMPC contracted the matrix and displayed receptor- and non-receptor-mediated contractility, indicating that BM-SMPC can generate force in response to vasoreactive agonists. We also prepared tissue-engineered blood vessels from BM-SMPC and BM-derived endothelial cells and implanted them into the jugular veins of lambs. As early as five weeks post-implantation, grafted tissues displayed a confluent endothelial layer overlaying the medial layer in which BM-SMPC were aligned circumferentially and synthesized significant amounts of collagen. In contrast to previous results with vascular SMC, BM-SMPC synthesized high amounts of elastin that was organized in a fibrillar network very similar to that of native vessels.

Conclusions Our results suggest that BM-SMPC may be useful in studying SMC differentiation and have high potential for development of cell therapies for the treatment of cardiovascular disease.

KEYWORDS Stem cells; Bone marrowSmooth muscle cells; Mesenchymal stem cells; Alpha actin promoter; Vascular tissue engineering; Ovine; Blood vessels; Transcriptional activation; Ovine animal model


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