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Abstract
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 that in vitro hMSCs appear to surround keratinocytes, and
this organization is recapitulated in 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.
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