Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

Abstract

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.

Effect of low oxygen tension on the biological characteristics of human bone marrow mesenchymal stem cells

“…Human mesenchymal stem cells (MSCs) possess enormous potential for tissue repair and renewal of damaged cells, which is attributed to their multipotent differentiative capacity (Sasaki et al 2008;Toma et al 2002), trophic activity (Caplan and Dennis 2006;Zhang et al 2007), potent immunosuppressive effects (Aggarwal and Pittenger 2005;Nauta and Fibbe 2007), and ability to induce vascularization (Martens et al 2006). These characteristics of MSCs make them promising therapeutic tools for use in the clinic.…”

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…This principle applies to all SCs that modulate inflammation and have a limited capacity to generate a specialized progeny. However, they indirectly activate resident SCs, enhancing the repair of the organ [70][71][72]. Because of these characteristics, therapeutically, MSCs and MSC-like SCs may have to be repeatedly employed to exert their role long-term, in absence of clear evidence of their homing and persistence inside the tissues [14][15][16][17][18][19][20].…”

PDGFRα-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia

“…BM can also generate epithelial cells, i.e., keratinocytes, in the epithelia, although the precise derivations and mechanisms to raise BM-derived keratinocytes are not fully known (3,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Human/mouse studies involving transplantation of sex-mismatched or genetically tagged BM cells have shown that keratin-positive bone marrow-derived cells can be found in skin epidermis, hair follicles, and sebaceous glands (6,8,9,11,12,14,16), sites that harbor skin stem cell niches (17). Moreover, in humans who have undergone BM transplantation (BMT), donor cells that have differentiated into keratinocytes can be detected in the epidermis for at least 3 y (8).…”