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Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Mesenchymal stem cells (MSCs) can differentiate not only into mesenchymal lineage cells but also into various other cell lineages. As MSCs can easily be isolated from bone marrow, they can be used in various tissue engineering strategies. In this study, we assessed whether MSCs can differentiate into multiple skin cell types including keratinocytes and contribute to wound repair. First, we found keratin 14-positive cells, presumed to be keratinocytes that transdifferentiated from MSCs in vitro. Next, we assessed whether MSCs can transdifferentiate into multiple skin cell types in vivo. At sites of mouse wounds that had been i.v. injected with MSCs derived from GFP transgenic mice, we detected GFP-positive cells associated with specific markers for keratinocytes, endothelial cells, and pericytes. Because MSCs are predominantly located in bone marrow, we investigated the main MSC recruitment mechanism. MSCs expressed several chemokine receptors; especially CCR7, which is a receptor of SLC/CCL21, that enhanced MSC migration. Finally, MSC-injected mice underwent rapid wound repaired. Furthermore, intradermal injection of SLC/CCL21 increased the migration of MSCs, which resulted in an even greater acceleration of wound repair. Taken together, we have demonstrated that MSCs contribute to wound repair via processes involving MSCs differentiation various cell components of the skin.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants-in-aid for Scientific Research (no. 13357008 to H.S. and no. 15790563 to R.A.) and the Project for Realization of Regenerative Medicine from the Ministry of Education, Science, Sports and Culture of Japan (to H.S.), and Health and Labor Sciences Research grants from the Ministry of Health, Labor and Welfare of Japan (no. H13-Measures for Intractable Disease-02 and H16-Measures for Intractable Disease-02 to H.S.).
2 M.S and R.A. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Hiroshi Shimizu, Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita-ku, Sapporo 060-8638, Japan. E-mail address: shimizu{at}med.hokudai.ac.jp
4 Abbreviations used in this paper: MSC, mesenchymal stem cell; FISH, fluorescence in situ hybridization; SMA, smooth muscle actin; TARC, thymus and activation regulated chemokine; MIP, macrophage inflammatory protein; SLC, secondary lymphoid tissue chemokine; CTACK, cutaneous T cell-attracting chemokine; HPF, high power field.
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