Sun Jin Baek

Kang SK, Ra JC

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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.

Keywords:

adipose tissue; cell migration assays; cell movement; chemokines; cytokines; mesenchymal stem cells; receptors, chemokine; receptors, cytokine

Abbreviations:

AdMSC, adipose tissue-derived mesenchymal stem cell; BCA-1, B-cell attracting chemokine-1; bFGF, basic fibroblast growth factor; BMMSC, bone marrow-derived mesenchymal stem cell; CCR, C-C chemokine receptor type; CXCL16, C-X-C motif chemokine 16; CXCR, C-X-C chemokine receptor type; FGFR1, fibroblast growth factor receptor 1; GF, growth factor; hAdMSC, human adipose tissue-derived mesenchymal stem cell; HGF, hepatocyte growth factor; IGF-1, insulin-like growth factor-1; IGF1R, insulin-like growth factor-1 receptor; MCP, monocyte chemotactic protein; MIP, macrophage inflammatory protein; MSC, mesenchymal stem cell; MT1-MMP, membrane type 1-matrix metalloproteinase; PBMC, peripheral blood mononuclear cell; PDGFRA, PDGF receptor A; PDGFRB, PDGF receptor B; SDF-1α, stromal-derived factor-1α; TGFBR2, TGF-β receptor 2; TNFRSF1A, TNF receptor superfamily, member 1A

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Experimental & Molecular Medicine

43, 596-603

2011

http://www.nature.com/emm/journal/v43/n10/full/emm201168a.html