Transdifferentiation of human endothelial progenitors into smooth muscle cells

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• 作者：HaYeun Ji^a ; ¹ ; Leigh Atchison^b ; ¹ ; Zaozao Chen^a ; Syandan Chakraborty^a ; Youngmee Jung^d ; George A. Truskey^b ; Nicolas Christoforou^b ; ^c ; ^{nicolas.christoforou@kustar.ac.ae" class="auth_mail" title="E-mail the corresponding author} ; ^{nc28@duke.edu" class="auth_mail" title="E-mail the corresponding author} ; Kam W. Leong^a ; ^{kwl2121@columbia.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Direct transdifferentiation ; Direct reprogramming ; Smooth muscle cell differentiation ; Myocardin ; Tissue-engineered blood vessel
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：85
• 期：Complete
• 页码：180-194
• 全文大小：4947 K

文摘

Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction.