The role of growth factors in maintenance of sternness in bone marrow-derived mesenchymal stem cells
The role of growth factors in maintenance of sternness in bone marrow-derived mesenchymal stem cells
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DOI：
10.1016/j.bbrc.2014.01.084
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发表时间：
2014-02-28
影响因子：
3.1
通讯作者：
Shim, Kwang Yong
中科院分区：
文献类型：
--
作者：
Eom, Young Woo;Oh, Ji-Eun;Shim, Kwang Yong
间充质干细胞（MSC）是再生医学研究的一个活跃课题，因为它们能够分泌多种生长因子和细胞因子，促进受损组织和器官的愈合。此外，这些分泌的生长因子和细胞因子已被证明可以通过调节MSC增殖和分化来发挥自分泌作用。我们发现，在骨髓间充质干细胞（BMSC）连续传代过程中，EGF、FGF-4 和 HGF 的表达下调。评估了用这些生长因子处理2个月的BMSC的增殖和分化潜力，并与用FGF-2处理的BMSC进行比较，FGF-2增加了BMSC的增殖。 FGF-2和-4在2个月内以高水平增加增殖潜力，分别约76倍和26倍，而EGF和HGF使BMSC的增殖增加不到2.8倍。有趣的是，分化潜力，尤其是脂肪生成，仅通过 HGF 处理才能维持。 FGF-2 处理迅速诱导 AICT 激活，随后诱导 ERK 激活。在用 FGF-2 处理的 BMSC 连续传代期间，磷酸化 ERK 的基础水平增加。在未处理的对照中，自噬标记物 LC3-II 的表达逐渐增加，并且在第 7 代时衰老细胞的数量急剧增加。但在长期（即 2 个月）培养过程中，FGF-2 和 FGF-4 抑制 LC3-II 表达并下调衰老细胞。总而言之，连续传代过程中生长因子的消耗可以通过抑制 ART 和 ERR 信号诱导自噬、衰老和干性下调（通过 FGF-2/-4 增殖和通过 HGF 分化）。 (C) 2014 年，爱思唯尔公司出版
Mesenchymal stem cells (MSCs) are an active topic of research in regenerative medicine due to their ability to secrete a variety of growth factors and cytokines that promote healing of damaged tissues and organs. In addition, these secreted growth factors and cytokines have been shown to exert an autocrine effect by regulating MSC proliferation and differentiation. We found that expression of EGF, FGF-4 and HGF were down-regulated during serial passage of bone marrow-derived mesenchymal stem cells (BMSCs). Proliferation and differentiation potentials of BMSCs treated with these growth factors for 2 months Were evaluated and compared to BMSCs treated with FGF-2, which increased proliferation of BMSCs. FGF-2 and -4 increased proliferation potentials at high levels, about 76- and 26-fold, respectively, for 2 months, while EGF and HGF increased proliferation of BMSCs by less than 2.8-fold. Interestingly, differentiation potential, especially adipogenesis, was maintained only by HGF treatment. Treatment with FGF-2 rapidly induced activation of AICT and later induced ERK activation. The basal level of phosphorylated ERK increased during serial passage of BMSCs treated with FGF-2. The expression of LC3-II, an autophagy marker, was gradually increased and the population of senescent cells was increased dramatically at passage 7 in non-treated controls. But FGF-2 and FGF-4 suppressed LC3-II expression and down-regulated senescent cells during long-term (i.e. 2 month) cultures. Taken together, depletion of growth factors during serial passage could induce autophagy, senescence and down-regulation of sternness (proliferation via FGF-2/-4 and differentiation via HGF) through suppression of ART and ERR signaling. (C) 2014 Published by Elsevier Inc.