Stem Cell Research Center RNL BIO Co., Ltd. Seoul, Korea.
Exp Mol Med. 2011 Oct 31;43(10):596-603. doi: 10.3858/emm.2011.43.10.069.
The homing properties of adipose tissue-derived mesenchymal stem cells (AdMSCs) have stimulated intravenous applications for their use in stem cell therapy. However, the soluble factors and corresponding cellular receptors responsible for inducing chemotaxis of AdMSCs have not yet been reported. In the present study, the migration capacity of human AdMSCs (hAdMSCs) toward various cytokines or growth factors (GFs) and the expression of their receptors were determined. In a conventional migration assay, PDGF-AB, TGF-β1, and TNF-α showed the most effective chemoattractant activity. When AdMSCs were preincubated with various chemokines or GF, and then allowed to migrate toward medium containing 10% FBS, those preincubated with TNF-α showed the highest migratory activity. Next, hAdMSCs were either preincubated or not with TNF-α, and allowed to migrate in response to various GFs or chemokines. Prestimulation with TNF-α increased the migration activity of hAdMSCs compared to unstimulated hAdMSCs. When analyzed by FACS and RT-PCR methods, hAdMSCs were found to express C-C chemokine receptor type 1 (CCR1), CCR7, C-X-C chemokine receptor type 4 (CXCR4), CXCR5, CXCR6, EGF receptor, fibroblast growth factor receptor 1, TGF-β receptor 2, TNF receptor superfamily member 1A, PDGF receptor A and PDGF receptor B at both the protein and the mRNA levels. These results indicate that the migration capacity of hAdMSCs is controlled by various GFs and chemokines. Prior in vitro modulation of the homing capacity of hAdMSCs could stimulate their movement into injured sites in vivo when administered intravenously, thereby improving their therapeutic potential.
脂肪组织来源的间充质干细胞（AdMSCs）的归巢特性刺激了其静脉应用于干细胞治疗。然而，诱导 AdMSCs 趋化的可溶性因子和相应的细胞受体尚未报道。在本研究中，测定了人 AdMSCs（hAdMSCs）对各种细胞因子或生长因子（GFs）的迁移能力及其受体的表达。在常规迁移测定中，PDGF-AB、TGF-β1 和 TNF-α 显示出最有效的趋化活性。当 AdMSCs 用各种趋化因子或 GF 预孵育，然后允许迁移到含有 10% FBS 的培养基中时，用 TNF-α 预孵育的细胞显示出最高的迁移活性。接下来，hAdMSCs 或用 TNF-α 预孵育，或不用 TNF-α 预孵育，然后响应各种 GFs 或趋化因子迁移。与未刺激的 hAdMSCs 相比，TNF-α 的预刺激增加了 hAdMSCs 的迁移活性。通过 FACS 和 RT-PCR 方法分析，发现 hAdMSCs 表达 C-C 趋化因子受体 1（CCR1）、CCR7、C-X-C 趋化因子受体 4（CXCR4）、CXCR5、CXCR6、EGF 受体、成纤维细胞生长因子受体 1、TGF-β 受体 2、TNF 受体超家族成员 1A、PDGF 受体 A 和 PDGF 受体 B 在蛋白质和 mRNA 水平上。这些结果表明 hAdMSCs 的迁移能力受各种 GFs 和趋化因子的控制。体外预先调节 hAdMSCs 的归巢能力，当静脉内给予时，可刺激其进入体内损伤部位，从而提高其治疗潜力。
