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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4551-4558.
Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-10-118273.
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Submitted October 17, 2007
Accepted February 4, 2008
Bone marrow derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature
Patrick Au, Joshua Tam, Dai Fukumura, and Rakesh K. Jain*
Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States
* Corresponding author; email: jain{at}steele.mgh.harvard.edu.
Vascular tissue engineering requires a ready source of endothelial cells and perivascular cells. Here, we evaluated human bone marrow-derived mesenchymal stem cells (hMSCs) for use as vascular progenitor cells in tissue engineering and regenerative medicine. hMSCs expressed a panel of smooth muscle markers in vitro including the cardiac/smooth muscle specific transcription co-activator, myocardin. Cell-cell contact between endothelial cells and hMSCs up-regulated the transcription of myocardin. hMSCs efficiently stabilized nascent blood vessels in vivo by functioning as perivascular precursor cells. The engineered blood vessels derived from human umbilical cord vein endothelial cells and hMSCs remained stable and functional for more than 130 days in vivo. On the other hand, we could not detect differentiation of hMSCs to endothelial cell in vitro and hMSCs by themselves could not form conduit for blood flow in vivo. Similar to normal perivascular cells, hMSCs-derived perivascular cells contracted in response to endothelin-1 in vivo. In conclusion, hMSCs are perivascular cell precursors and may serve as an attractive source of cells for use in vascular tissue engineering and for the study of perivascular cell differentiation.
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