Fabrication of vascular smooth muscle-like tissues based on self-organization of circumferentially aligned cells in microengineered hydrogels
Fabrication of vascular smooth muscle-like tissues based on self-organization of circumferentially aligned cells in microengineered hydrogels
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基于微工程水凝胶中圆周排列细胞的自组织制造血管平滑肌样组织
DOI：
10.1039/d0lc00544d
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发表时间：
2020-09-07
期刊：
影响因子：
6.1
通讯作者：
Fukuda, Toshio
中科院分区：
文献类型：
--
作者：
Sun, Tao;Shi, Qing;Fukuda, Toshio
血管平滑肌细胞（vSMC）的周向排列对于在体外形成体内样血管平滑肌层至关重要。尽管已经证明了在3D基底上引起这种对齐的许多技术，但在3D水凝胶中概括血管平滑肌组织的周向细胞对齐仍然是一个挑战。在这里，我们提出了一个弹簧状明胶甲基丙烯酸酯（GelMA）的结构形成的半自动缫丝的核-壳微纤维在微米级。所得到的结构有利于封装的人间充质干细胞（MSC）的周向排列和自组织成多层弹簧状细胞结构。基于这些结构的可渗透管腔，开发了灌注培养微系统，以进一步促进MSC在TGF-β 1作用下的vSMC分化。我们还评估了MSC收缩诱导的细胞结构收缩。这些结果证明了在3D环境中血管平滑肌（vSM）样组织的成功体外再生。与基质表面相比，水凝胶中的多孔结构更接近于体内的细胞微环境。因此，该方法可用于建立研究高血压血管组织再生和血管重塑机制的体外模型。
Circumferential alignment of vascular smooth muscle cells (vSMCs) is critical to form an in vivo-like vascular smooth muscle layer in vitro. Although many techniques to elicit such an alignment on 3D substrates have been demonstrated, it remains a challenge to recapitulate the circumferential cellular alignment of vascular smooth muscle tissues in 3D hydrogels. Here, we propose a spring-like gelatin methacrylate (GelMA) structure formed by semi-automated reeling of a core-shell microfiber at the microscale. The resulting structures facilitate circumferential alignment and self-organization of encapsulated human mesenchymal stem cells (MSCs) into multilayer spring-like cellular structures. Based on the permeable tubular lumens of these structures, a perfusion culture micro-system is developed to further facilitate the vSMC differentiation of MSCs under the effect of TGF-beta 1. We also evaluated the MSC contraction-induced shrinkage of the resulting cellular structures. These results demonstrate the successful in vitro regeneration of vascular smooth muscle (vSM)-like tissues in 3D environments. Compared with the substrate surface, the porous structure in hydrogels is more similar to cell microenvironments in vivo. Thus, this approach may be used to develop an in vitro model for the study of vascular tissue regeneration and the mechanism of vascular remolding during hypertension.