A novel method for differentiation of human mesenchymal stem cells into smooth muscle-like cells on clinically deliverable thermally induced phase separation microspheres.
A novel method for differentiation of human mesenchymal stem cells into smooth muscle-like cells on clinically deliverable thermally induced phase separation microspheres.
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DOI：
10.1089/ten.tec.2014.0431
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
N. Parmar;R. Ahmadi;R. Day
中科院分区：
文献类型：
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作者：
N. Parmar;R. Ahmadi;R. Day
肌肉退化是一种普遍的疾病，特别是在老龄化社会，它对生活质量有巨大的影响，并产生巨大的健康成本。平滑肌细胞的合适供体来源是有限的，并且寻求通过将细胞递送到肌肉的受损或退化区域来增加肌肉体积的微创治疗方法。对于第一次，我们报告使用热诱导相分离（TIPS）产生的高度多孔的微载体，以扩大和分化脂肪间充质干细胞（AdMSCs）成平滑肌样细胞的格式，需要最小的操作之前，临床交付。AdMSCs可以很容易地附着在TIPS微载体的表面，并在悬浮培养12天后增殖。将孵育培养基转换为含有2 ng/mL转化生长因子β-1的分化培养基导致细胞收缩器组分钙调蛋白、钙调蛋白和肌球蛋白重链的mRNA和蛋白表达显著增加，表明平滑肌细胞样表型。平滑肌细胞在微载体表面上的生长不会改变聚合物微球的完整性，使其适合于细胞递送载体。我们的研究结果表明，TIPS微球提供了一个理想的基板的扩增和分化成平滑肌样细胞的AdMSCs，以及为准备用于治疗应用的附着细胞的微载体递送车辆。
Muscle degeneration is a prevalent disease, particularly in aging societies where it has a huge impact on quality of life and incurs colossal health costs. Suitable donor sources of smooth muscle cells are limited and minimally invasive therapeutic approaches are sought that will augment muscle volume by delivering cells to damaged or degenerated areas of muscle. For the first time, we report the use of highly porous microcarriers produced using thermally induced phase separation (TIPS) to expand and differentiate adipose-derived mesenchymal stem cells (AdMSCs) into smooth muscle-like cells in a format that requires minimal manipulation before clinical delivery. AdMSCs readily attached to the surface of TIPS microcarriers and proliferated while maintained in suspension culture for 12 days. Switching the incubation medium to a differentiation medium containing 2 ng/mL transforming growth factor beta-1 resulted in a significant increase in both the mRNA and protein expression of cell contractile apparatus components caldesmon, calponin, and myosin heavy chains, indicative of a smooth muscle cell-like phenotype. Growth of smooth muscle cells on the surface of the microcarriers caused no change to the integrity of the polymer microspheres making them suitable for a cell-delivery vehicle. Our results indicate that TIPS microspheres provide an ideal substrate for the expansion and differentiation of AdMSCs into smooth muscle-like cells as well as a microcarrier delivery vehicle for the attached cells ready for therapeutic applications.