Concise review: bone marrow-derived stem/progenitor cells in cutaneous repair and regeneration

Abstract

Our understanding of the role of bone marrow (BM)-derived cells in cutaneous homeostasis and wound healing had long been limited to the contribution of inflammatory cells. Recent studies, however, suggest that the BM contributes a significant proportion of noninflammatory cells to the skin, which are present primarily in the dermis in fibroblast-like morphology and in the epidermis in a keratinocyte phenotype; and the number of these BM-derived cells increases markedly after wounding. More recently, several studies indicate that mesenchymal stem cells derived from the BM could significantly impact wound healing in diabetic and nondiabetic animals, through cell differentiation and the release of paracrine factors, implying a profound therapeutic potential. This review discusses the most recent understanding of the contribution of BM-derived noninflammatory cells to cutaneous homeostasis and wound healing.

Figure 1

Bone marrow-derived mesenchymal stem cells (BM-MSCs) in cutaneous regeneration. (A, B): Keratinocytes loaded on a collagen gel containing BM-MSCs formed rete ridge-like structure, whereas keratinocytes loaded on a collagen gel containing dermal fibroblasts did not. Images adapted from Aoki et al. [58]. Image courtesy of Molecular Biology of the Cell. (C): BM-MSCs (green) from GFP-expressing mice were injected around the excisional wound and applied on the wound bed in Matrigel in Balb/C mice. At day 7, some mesenchymal stem cells (yellow) expressed keratinocyte marker cytokeratins (red) and formed structures similar to those observed in the study of Aoki et al. (A). Abbreviations: BMSC, bone morrow-derived mesenchymal stem cells; H&E, hematoxylin and eosin stain.

Figure 2

Paracrine effect of Bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing. BM-MSCs (green) in a cutaneous wound release growth factors such as IGF-1, EGF, and KGF to promote the proliferation of keratinocytes, release proangiogenic cytokines such as VEGF-a and Ang-1 to enhance angiogenesis, release chemokines such as MIP-1 to recruit monocytes into the wound, and release cytokines such as SDF-1 and G-CSF to recruit EPCs into the wound. Abbreviations: ang-1, angiopoietin-1; EGF, epidermal growth factor; EPC, endothelial progenitor cell; FB, fibroblast; G-CSF, granulocyte colony-stimulating factor; IGF, insulin-like growth factor; KGF, keratinocyte growth factor; MIP-1, macrophage inflammatory protein-1; MSC, mesenchymal stem cell; SDF1, Stromal cell-derived factor-1; VEGF, vascular endothelial growth factor.