Doğan Ayşegül, Şenkal-Turhan Selinay, Bulut-Okumuş Ezgi
Faculty of Engineering, Genetics and Bioengineering Department, Yeditepe University, İstanbul, Türkiye.
Faculty of Engineering, Genetics and Bioengineering Department, Yeditepe University, İstanbul, Türkiye.
Biochimie. 2025 Sep;236:104-116. doi: 10.1016/j.biochi.2025.06.016. Epub 2025 Jun 26.
Derivation of adult mesenchymal stem cells (MSCs) from induced pluripotent stem cells (iPSCs) in culture might be an important approach to generate unlimited cell source for clinical therapies. Identification of appropriate progenitor populations during development is of interest in recent years to establish accurate steps in cell differentiation protocols. In the current study, iPSC derived MSCs (iMSC) via neuromesodermal progenitors (NMP) were generated using an established in vitro differentiation protocol. Osteogenic and adipogenic differentiation potential of iMSCs were evaluated by in vitro cell culture assays, gene and protein expression analysis. Protein expression profile of iMSCs and secretome of iMSCs were determined by membrane array and LC-MS/MS analysis. Conditioned medium derived from iMSCs was used in differentiation protocol of preadipocytes and preosteoblast cells. Adipogenic and osteogenic cells were derived from iMSCs in vitro. Protein profile of iMSCs were different compared to dental pulp and adipose stem cells. iMSC secretome has a more prominent role to promote adipogenesis in cultured preadipocytes. In conclusion, MSCs with an adipogenic and osteogenic differentiation capacity can be obtained from iPSC derived NMPs in vitro. Secretome of iMSCs have adiponenic potential on preadipocytes and can be a promising option for future studies.
在培养过程中从诱导多能干细胞（iPSC）中获得成人间充质干细胞（MSC）可能是为临床治疗生成无限细胞来源的重要途径。近年来，在发育过程中鉴定合适的祖细胞群体对于确立细胞分化方案中的准确步骤很有意义。在本研究中，使用既定的体外分化方案，通过神经中胚层祖细胞（NMP）生成了iPSC来源的MSC（iMSC）。通过体外细胞培养试验、基因和蛋白质表达分析评估了iMSC的成骨和成脂分化潜能。通过膜阵列和液相色谱 - 串联质谱分析确定了iMSC的蛋白质表达谱和iMSC的分泌组。源自iMSC的条件培养基用于前脂肪细胞和前成骨细胞的分化方案。在体外从iMSC中获得了成脂和成骨细胞。与牙髓和脂肪干细胞相比，iMSC的蛋白质谱有所不同。iMSC分泌组在促进培养的前脂肪细胞成脂方面具有更显著的作用。总之，具有成脂和成骨分化能力的MSC可以在体外从iPSC来源的NMP中获得。iMSC的分泌组对前脂肪细胞具有促脂肪生成的潜力，可能是未来研究的一个有前景的选择。
