“…The main concerns of cell therapy are limited replicative lifespan, risk of teratoma formation after transplantation, and ethical issues . Eukaryotic cells can be considered as robust natural bioreactors that produce a variety of bioactive molecules with the appropriate ratio, which can act as therapeutic agents in the wound-healing process and enhance the regeneration rate of the lost/damaged tissue. − Furthermore, recent investigations have revealed that multipotent, plastic mesenchymal stem cells (MSCs), which benefit from paracrine signaling, are highly potent to be utilized as allogenic sources for enhancing wound healing. , Paracrine signaling contributes to the regenerative ability of MSCs either through the whole secretome or even through the exosomes; this signaling has been reported to be effective in wound healing and scar reduction through modulating the ratios of MMP-3/TIMP1, TGF-β3/TGF-β1, and (type III collagen)/(type I collagen), which reduce the myofibroblast differentiation and eventually promote ECM reconstruction and wound healing . As natural bioreactors, MSCs secrete lots of bioactive molecules, which could accelerate wound healing by increasing the migration of the dermal fibroblast and keratinocyte into the wound area, resulting in accelerated wound healing. , MSCs also increase the level of angiogenesis via increasing the levels of VEFG and HGF, increasing the microvessel density, and improving the microcirculation in the wound. , The immunomodulatory features of the MSCs can be harnessed to modulate the immune responses and inflammation .…”