The in vitro migration capacity of human bone marrow mesenchymal stem cells:: Comparison of chemokine and growth factor chemotactic activities
The in vitro migration capacity of human bone marrow mesenchymal stem cells:: Comparison of chemokine and growth factor chemotactic activities
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DOI：
10.1634/stemcells.2007-0054
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发表时间：
2007-07-01
期刊：
影响因子：
5.2
通讯作者：
Domenech, Jorge
中科院分区：
文献类型：
--
作者：
Lopez Ponte, Adriana;Marais, Emeline;Domenech, Jorge
成人骨髓来源的干细胞，包括造血干细胞和骨髓间充质干细胞，是修复许多受损组织的重要细胞来源。与HSC相比，能够诱导MSC迁移的可溶性因素还没有得到广泛的研究。在本工作中，我们比较了预育或未预育的人骨髓间充质干细胞在炎性细胞因子白介素1-6(IL-1β)和肿瘤坏死因子-α(TNF-α)作用下对16种生长因子(GFS)和趋化因子的体外迁移能力。我们发现骨髓间充质干细胞在多种趋化因子的作用下迁移。而趋化因子RANTES、巨噬细胞源性趋化因子(MDC)和基质衍生因子-1(SDF-1)的作用有限。值得注意的是，与TNFa预先孵育导致MSC向趋化因子迁移增加，而向大多数GFS迁移没有变化。与这些结果一致的是，骨髓间充质干细胞表达酪氨酸激酶受体PDGF-受体(R)a、PDGF-R 3和IGF-R，以及RANTES和MDC受体CCR2、CCR3和CCR4以及SDF-1受体CXCR4。TNFa增加CCR2、CCR3和CCR4的表达(与CXCR4相反)，并与RANTES膜结合。提示骨髓间充质干细胞的迁移能力受多种受体酪氨酸激酶GFS和CC、CXC趋化因子的调控。大多数趋化因子对肿瘤坏死因子α诱导的细胞更有效。我们的结果提示，MSCs的动员和随后对损伤组织的归巢可能取决于全身和局部的炎症状态。
Adult bone marrow (BM)-derived stem cells, including hernatopoietic stem cells (HSCs) and MSCs, represent an important source of cells for the repair of a number of damaged tissues. In contrast to HSCs, the soluble factors able to induce MSC migration have not been extensively studied. In the present work, we compared the in vitro migration capacity of human BM-derived MSCs, preincubated or not with the inflammatory cytokines interleukin 1,6 (IL1 beta) and tumor necrosis factor a (TNF alpha), in response to 16 growth factors (GFs) and chemokines. We show that BM MSCs migrate in response to many chemotactic factors. The GFs platelet-derived growth factor-AB (PDGF-AB) and insulin-like growth factor 1 (IGF-1) are the most potent, whereas the chemokines RANTES, macrophage-derived chemokine (MDC), and stromall-derived factor-1 (SDF-1) have limited effect. Remarkably, preincubation with TNFa leads to increased MSC migration toward chemokines, whereas migration toward most GFs is unchanged. Consistent with these results, BM MSCs express the tyrosine kinase receptors PDGF-receptor (R) a, PDGF-R)3, and IGF-R, as well as the RANTES and MDC receptors CCR2, CCR3, and CCR4 and the SDF-1 receptor CXCR4. TNFa increases CCR2, CCR3, and CCR4 expression (as opposed to that of CXCR4), together with RANTES membrane binding. These data indicate that the migration capacity of BM MSCs is under the control of a large range of receptor tyrosine kinase GFs and CC and CXC chemokines. Most chemokines are more effective on TNF alpha-primed cells. Our results suggest that the mobilization of MSCs and their subsequent homing to injured tissues may depend on the systemic and local inflammatory state.