Vascularization and restoration of heart function in rat myocardial infarction using transplantation of human cbMSC/HUVEC core-shell bodies

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• 作者：Wen-Yu Lee^a ; ¹ ; Hao-Ji Wei^b ; ¹ ; Jiun-Jie Wang^c ; ^d ; ¹ ; Kun-Ju Lin^c ; ^e ; Wei-Wen Lin^f ; Ding-Yuan Chen^a ; Chieh-Cheng Huang^a ; Ting-Yin Lee^a ; Hsiang-Yang Ma^g ; Shiaw-Min Hwang^h ; Yen Chang^b ; ^{ychang@vghtc.gov.tw} ; Hsing-Wen Sung^a ; ^{hwsung@che.nthu.edu.tw}
• 关键词：Thermo-responsive hydrogel ; Vasculogenesis ; Blood perfusion ; Cell therapy ; Cardiac regeneration ; Thermo-responsive hydrogel
• 刊名：Biomaterials
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：33
• 期：7
• 页码：2127-2136
• 全文大小：2474 K

文摘

Cell transplantation is a promising strategy for therapeutic treatment of ischemic heart diseases. In this study, cord blood mesenchymal stem cells (cbMSCs) and human umbilical vein endothelial cells (HUVECs) in the form of core-shell bodies (cbMSC/HUVEC bodies) were prepared to promote vascularization and restore heart functions in an experimentally-created myocardial infarction (MI) rat model. Saline, cbMSC bodies and HUVEC bodies were used as controls. In?vitro results indicated that cbMSC/HUVEC bodies possessed the capability of heterotypic assembly of cbMSCs and HUVECs into robust and durable tubular networks on Matrigel. The up-regulated gene expressions of VEGF and IGF-1 reflected the robust expansion of tubular networks; in addition, the augmented levels of SMA and SM22 suggested smooth muscle differentiation of cbMSCs, possibly helping to improve the durability of networks. Moreover, according to the in?vivo echocardiographic, magnetic resonance and computed-tomographic results, transplantation of cbMSC/HUVEC bodies benefited post-MI dysfunction. Furthermore, the vascularization analyses demonstrated the robust vasculogenic potential of cbMSC/HUVEC bodies in?vivo, thus contributing to the greater viable myocardium and the less scar region, and ultimately restoring the cardiac function. The concept of core-shell bodies composed of perivascular cells and endothelial cells may serve as an attractive cell delivery vehicle for vasculogenesis, thus improving the cardiac function significantly.