A Conditioned Medium of Umbilical Cord Mesenchymal Stem Cells Overexpressing Wnt7a Promotes Wound Repair and Regeneration of Hair Follicles in Mice

Abstract

Mesenchymal stem cells (MSCs) can affect the microenvironment of a wound and thereby accelerate wound healing. Wnt proteins act as key mediators of skin development and participate in the formation of skin appendages such as hair. The mechanisms of action of MSCs and Wnt proteins on skin wounds are largely unknown. Here, we prepared a Wnt7a-containing conditioned medium (Wnt-CM) from the supernatant of cultured human umbilical cord-MSCs (UC-MSCs) overexpressing Wnt7a in order to examine the effects of this CM on cutaneous healing. Our results revealed that Wnt-CM can accelerate wound closure and induce regeneration of hair follicles. Meanwhile, Wnt-CM enhanced expression of extracellular matrix (ECM) components and cell migration of fibroblasts but inhibited the migratory ability and expression of K6 and K16 in keratinocytes by enhancing expression of c-Myc. However, we found that the CM of fibroblasts treated with Wnt-CM (HFWnt-CM-CM) can also promote wound repair and keratinocyte migration; but there was no increase in the number of hair follicles of regeneration. These data indicate that Wnt7a and UC-MSCs have synergistic effects: they can accelerate wound repair and induce hair regeneration via cellular communication in the wound microenvironment. Thus, this study opens up new avenues of research on the mechanisms underlying wound repair.

Optimization of lentiviral transduction parameters and its application for CRISPR-based secretome modification of human endometrial mesenchymal stem cells

“…Probably, the underlying cause of the adverse effects of Pb + LV infection on MSCs proliferation rate observed previously by other authors might also be cell senescence [23]. Of note, in the modern studies, Pb is actively used to increase the effectiveness of MSCs transduction for either purpose, what with regard to our results may somehow distort the data obtained by the authors [57][58][59][60].…”

“…Additionally, Flt-1-engineered MSCs caused regression of endometriotic lesions [50]. A plenty of other fascinating results are obtained by applying MSCs with genetically modified paracrine activity [57,58,63,64]. However, in the vast majority of studies, the gain-of-function genetic perturbations are obtained by the use of cDNA overexpression systems.…”

Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases

“…Moreover, Wnt7a and Wnt7b, which are negatively regulated by bone morphogenetic protein, maintain hair follicle stem cell homeostasis and promotes hair follicle regeneration . Wnt7a‐containing media from Wnt7a‐transfected umbilical cord mesenchymal stem cells promote wound repair and induce hair follicle regeneration . Through Wnt7a/β‐catenin pathway, vitamin A activates hair follicle stem cells to promote growth phase of the hair cycle within the hair follicle bulge .…”

“…66,67 Wnt7a-containing media from Wnt7a-transfected umbilical cord mesenchymal stem cells promote wound repair and induce hair follicle regeneration. 68 Through Wnt7a/ β-catenin pathway, vitamin A activates hair follicle stem cells to promote growth phase of the hair cycle within the hair follicle bulge. 69 Interestingly, Wnt7a seems to be involved in pigmentation of the regenerated hairs by affecting melanocyte stem cells.…”

The Potential of a Hair Follicle Mesenchymal Stem Cell-Conditioned Medium for Wound Healing and Hair Follicle Regeneration

“…Skin injuries are the most commonly found injury caused by blisters, burns, cuts, and ulcers of various severities [1]. If left untreated, any skin injury can interfere with its protective function and cause body tissues to be easily exposed to mechanical damages and microbial infections [2].…”