Keratinocyte Induced Differentiation of Mesenchymal Stem Cells into Dermal Myofibroblasts: A Role in Effective Wound Healing.
We have previously demonstrated that human mesenchymal stem cells (hMSCs) migrate toward human keratinocytes as well as toward conditioned medium from cultured human keratinocytes (KCM) indicating that the hMSCs respond to signals from keratinocytes [1]. Using fluorescently labeled cells we now show thatin vitrohMSCs appear to surround keratinocytes, and this organization is recapitulatedin vivo. Incubation of hMSCs with KCM induced dermal myofibroblast like differentiation characterized by expression of cytoskeletal markers and increased expression of cytokines including SDF-1, IL-8, IL-6 and CXCL5. Interaction of keratinocytes with hMSCs appears to be important in the wound healing process. Therapeutic efficacy of hMSCs in wound healing was examined in two animal models representing normal and chronic wound healing. Accelerated wound healing was observed when hMSCs and KCM exposed hMSCs (KCMSCs) were injected near wound site in nude and NOD/SCID mice. Long term follow up of wound healing revealed that in the hMSC treated wounds there was little evidence of residual scarring. These dermal myofibroblast like hMSCs add to the wound healing process. Together, the keratinocyte and hMSCs morphed dermal myofibroblast like cells as well as the factors secreted by these cells support wound healing with minimal scarring. The ability of hMSCs to support wound healing process represents another striking example of the importance of keratinocyte and hMSCs interplay in the wound microenvironment resulting in effective wound healing with minimal scarring.
Intermountain Precision Genomics, Intermountain Healthcare, Dixie Regional Medical Center 292 South 1470 East, Suite 201 & 301, St. George, UT 84770, USA.
Pravin J
PJ
Mishra
Department of Biochemical and Cellular Pharmacology, Genentech, 1, DNA Way, South San Francisco, California 94080, USA.
Prasun J
PJ
Mishra
Department of Pharmacology, Robert Wood Johnson Medical School, Graduate School of Biomedical Sciences, New Brunswick-Piscataway, Rutgers University, 675 Hoes Lane West, Piscataway, NJ 08854. USA.
Debabrata
D
Banerjee
Mesenchymal stem cells; animal models; cytokine secretion; dermal myofibroblast; keratinocyte conditioned medium; scarring; wound healing