Abstract
As tissue engineering and regenerative medicine have evolved recently, stem cell therapy has been investigated in the field of impaired wound healing. Several studies have reported that mesenchymal stem cells derived from various tissues including bone marrow and adipose tissue can exert the regenerative efficacy in the wound healing. Previously, we have demonstrated the isolation and characterization of tonsil-derived mesenchymal stem cells (TMSCs) with excellent proliferative property. In the present study, we aimed to evaluate the regenerative efficacy of TMSCs in the wound healing process. Two distinct cutaneous surgical defects were generated in the dorsum of mice. Each wound was treated with TMSCs or phosphate-buffered saline (PBS), respectively. After sacrifice, the skin and subcutaneous tissues around the surgical defect were harvested and assessed for inflammation, re-epithelialization, dermal regeneration, and granulation tissue formation. The administration of TMSCs into wound beds significantly promoted the repair of surgical defects in mice. Especially, TMSCs efficiently contributed to the attenuation of excessive inflammation in the surgical lesion, as well as the augmentation of epidermal and dermal regeneration. To elucidate the underlying mechanisms, TMSCs were analyzed for their potency in immunomodulatory ability on immune cells, stimulatory effect on the proliferation of keratinocytes, and fibroblasts, as well as the regulation of fibroblast differentiation. TMSCs inhibited the non-specific or T-cell-specific proliferation of peripheral blood mononuclear cells, as well as the M1 polarization of macrophage-like cells. Moreover, TMSCs augmented the proliferation of skin-constituting fibroblasts and keratinocytes while they suppressed the differentiation of fibroblasts into myofibroblasts. Taken together, our findings demonstrate the regenerative potential of TMSCs in wound healing process through the regulation on inflammation, proliferation, and remodeling of various skin cells, implying that TMSCs can be a promising alternative for wound repair.
Highlights
Wound healing process is initiated in response to various deleterious stimuli to restore the tissue homeostasis as well as to limit further damage[1,2]
One million tonsil-derived mesenchymal stem cells (TMSCs) were placed on the wound beds after wound generation and the reduction rate of wound area was measured every other day until day 12
Because in vivo TMSC transplantation attenuated the infiltration of inflammatory cells, we explored the effect of TMSCs on the proliferation of inflammatory cells using peripheral blood mononuclear cells (PBMCs)
Summary
Wound healing process is initiated in response to various deleterious stimuli to restore the tissue homeostasis as well as to limit further damage[1,2]. It is a highly organized, well-controlled procedure which consists of somewhat overlapping but specific stages: inflammation, proliferation, and maturation/remodeling[3]. Some surgical techniques including skin graft and flaps have been tried to treat the delayed- or non-healing wound in combination with general symptomatic management (e.g. anti-inflammatory agent and pain reducer)[9,10], the therapeutic outcome is often limited with low functional recovery score. Given that disrupted cellular homeostasis, including persistent inflammation, excessive fibrosis, and decreased angiogenesis underlies chronic wound formation, more comprehensive approaches are required for complete wound repair
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