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在旋转生物反应器中,通过机械刺激,使人体间充质干细胞在血管细胞外基质支架上现场向血管细胞分化,从而构建血管移植物。

Vessel graft fabricated by the on-site differentiation of human mesenchymal stem cells towards vascular cells on vascular extracellular matrix scaffold under mechanical stimulation in a rotary bioreactor.

机构信息

Department of Biomedical Engineering, University of South Dakota, 4800 N Career Ave, Suite 221, Sioux Falls, SD, USA.

出版信息

J Mater Chem B. 2019 Apr 28;7(16):2703-2713. doi: 10.1039/c8tb03348j. Epub 2019 Mar 26.

Abstract

Although a significant number of studies on vascular tissue engineering have been reported, the current availability of vessel substitutes in the clinic remains limited mainly due to the mismatch of their mechanical properties and biological functions with native vessels. In this study, a novel approach to fabricating a vessel graft for vascular tissue engineering was developed by promoting differentiation of human bone marrow mesenchymal stem cells (MSCs) into endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) on a native vascular extracellular matrix (ECM) scaffold in a rotary bioreactor. The expression levels of CD31 and vWF, and the LDL uptake capacity as well as the angiogenesis capability of the EC-like cells in the dynamic culture system were significantly enhanced compared to the static system. In addition, α-actin and smoothelin expression, and contractility of VSMC-like cells harvested from the dynamic model were much higher than those in a static culture system. The combination of on-site differentiation of stem cells towards vascular cells in the natural vessel ECM scaffold and maturation of the resulting vessel construct in a dynamic cell culture environment provides a promising approach to fabricating a clinically applicable vessel graft with similar mechanical properties and physiological functions to those of native blood vessels.

摘要

尽管已经有大量关于血管组织工程的研究报告,但目前临床上可用的血管替代品仍然有限,主要是由于它们的机械性能和生物功能与天然血管不匹配。在这项研究中,通过在旋转生物反应器中促进人骨髓间充质干细胞(MSCs)向内皮细胞(ECs)和血管平滑肌细胞(VSMCs)分化,在天然血管细胞外基质(ECM)支架上开发了一种用于血管组织工程的新型血管移植物制造方法。与静态系统相比,动态培养系统中 EC 样细胞的 CD31 和 vWF 表达水平、LDL 摄取能力以及血管生成能力显著增强。此外,从动态模型中收获的 VSMC 样细胞的α-肌动蛋白和平滑肌蛋白表达和收缩性明显高于静态培养系统。在天然血管 ECM 支架中就地分化干细胞为血管细胞,以及在动态细胞培养环境中成熟所得血管构建体的组合,为制造具有类似于天然血管的机械性能和生理功能的临床应用血管移植物提供了一种很有前途的方法。

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