Wang Meng, Lin Shigang, Mequanint Kibret
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada.
Polymers (Basel). 2022 Apr 11;14(8):1555. doi: 10.3390/polym14081555.
Mesenchymal stem cells, derived from human-induced pluripotent stem cells (iPSC), are valuable for generating smooth muscle cells (SMCs) for vascular tissue engineering applications. In this study, we synthesized biodegradable α-amino acid-substituted poly(organophosphazene) polymers and electrospun nano-fibrous scaffolds (~200 nm diameter) to evaluate their suitability as a matrix for differentiation of iPSC-derived mesenchymal stem cells (iMSC) into mature contractile SMCs. Both the polymer synthesis approach and the electrospinning parameters were optimized. Three types of cells, namely iMSC, bone marrow derived mesenchymal stem cells (BM-MSC), and primary human coronary artery SMC, attached and spread on the materials. Although L-ascorbic acid (AA) and transforming growth factor-beta 1 (TGF-β1) were able to differentiate iMSC along the smooth muscle lineage, we showed that the electrospun fibrous mats provided material cues for the enhanced differentiation of iMSCs. Differentiation of iMSC to SMC was characterized by increased transcriptional levels of early to late-stage smooth muscle marker proteins on electrospun fibrous mats. Our findings provide a feasible strategy for engineering functional vascular tissues.
源自人诱导多能干细胞（iPSC）的间充质干细胞，对于生成用于血管组织工程应用的平滑肌细胞（SMC）具有重要价值。在本研究中，我们合成了可生物降解的α-氨基酸取代的聚有机膦腈聚合物，并通过静电纺丝制备了纳米纤维支架（直径约200纳米），以评估它们作为将iPSC衍生的间充质干细胞（iMSC）分化为成熟收缩性SMC的基质的适用性。聚合物合成方法和静电纺丝参数均得到了优化。三种类型的细胞，即iMSC、骨髓来源的间充质干细胞（BM-MSC）和原代人冠状动脉SMC，均附着并铺展在这些材料上。尽管L-抗坏血酸（AA）和转化生长因子-β1（TGF-β1）能够使iMSC沿着平滑肌谱系分化，但我们表明，静电纺丝纤维垫为iMSC的增强分化提供了材料线索。iMSC向SMC的分化表现为在静电纺丝纤维垫上早期至晚期平滑肌标记蛋白转录水平的增加。我们的研究结果为工程化功能性血管组织提供了一种可行的策略。
