PI3K/AKT/mTOR通路
间充质干细胞
蛋白激酶B
细胞生物学
细胞周期
细胞生长
P70-S6激酶1
再生医学
化学
干细胞
癌症研究
转化生长因子
信号转导
细胞
生物
生物化学
作者
Jie Sun,Yan Zhou,Zhaoyang Ye,Wen‐Song Tan
标识
DOI:10.1080/03008207.2019.1570171
摘要
Background: Mesenchymal stem cells (MSCs) are promising for cell therapy and regenerative medicine. An increased need for expanding of MSCs under serum-free condition to achieve a sufficient quantity for therapeutic applications is inevitable. Transforming growth factor-β1 (TGF-β1) is widely used for expanding clinical-grade MSCs in vitro. This work focuses on the influence of TGF-β1 on proliferation in rat bone marrow-derived MSCs (BMSCs) and the underlying mechanism. Materials and Methods: BMSCs were isolated and cultured with or without TGF-β1 in a serum-free medium and Cell Counting Kit-8 assay was used to detect BMSCs proliferation. Cell cycle transition was also analyzed. Further, the expression levels of cyclin D1, phosphorylated focal adhesion kinase, and downstream effectors in Akt-mTOR-S6K1 signaling pathway were examined by western blotting. Results and Conclusion: TGF-β1 triggered proliferation via accelerating G1/S cell cycle transition in BMSCs. The addition of TGF-β1 can activate Akt-mTOR-S6K1 pathway. Additionally, FAK was found to be involved in the process. Upon adding the FAK inhibitor, both the activation of Akt-mTOR-S6K1 and TGF-β1-induced cell proliferation were abrogated. Together, an insight understanding of how TGF-β1 influences BMSCs proliferation is achieved. This study provides a possible strategy of supplementing TGF-β1 in serum-free medium for in vitro expansion, which eventually would advance the production of clinical-grade MSCs for regenerative medicine.
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