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Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs)

Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs),10.1096/fj.07-087924,Faseb Journal,Zhaodi Gong,Lau

Small-diameter human vessel wall engineered from bone marrow-derived mesenchymal stem cells (hMSCs)   (Citations: 39)
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Using biodegradable scaffold and a bio- mimetic perfusion system, our lab has successfully engineered small-diameter vessel grafts using endothe- lial cells (ECs) and smooth muscle cells (SMCs) ob- tained from vessels in various species. However, trans- lating this technique into humans has presented tremendous obstacles due to species and age differ- ences. SMCs from elderly persons have limited prolif- erative capacity and a reduction in collagen production, which impair the mechanical strength of engineered vessels. As an alternative cell source, adult human bone marrow-derived mesenchymal stem cells (hMSCs) were studied for their ability to differentiate into SMCs in culture plates as well as in a bioreactor system. In the former setting, immunofluorescence staining showed that MSCs, after induction for 14 days, expressed smooth muscle -actin (SMA) and calponin, early and mid-SMC phenotypic markers, respectively. In the lat- ter setting, vessel walls were constructed with MSC- derived SMCs. Various factors (i.e., matrix proteins, soluble factors, and cyclic strain) in the engineering system were further investigated for their effects on hMSC cell proliferation and differentiation into SMCs. Based on a screening of multiple factors, the engineer- ing system was optimized by dividing the vessel culture into proliferation and differentiation phases. The ves- sel walls engineered under the optimized conditions were examined histologically and molecularly, and found to be substantially similar to native vessels. In conclusion, bone marrow-derived hMSCs can serve as a new cell source of SMCs in vessel engineering. Optimi- zation of the culture conditions to drive SMC differen- tiation and matrix production significantly improved the quality of the hMSC-derived engineered vessel wall.—Gong, Z., Niklason, L. E. Small-diameter human vessel wall engineered from bone marrow-derived mes- enchymal stem cells (hMSCs). FASEB J. 22, 000-000 (2008)
Journal: Faseb Journal - FASEB J , vol. 22, no. 6, pp. 1635-1648, 2008
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