Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs) onto the human acellular amniotic membrane (AAM). The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration.
Experiments with 5'-azacytidine and hematopoietic growth factor approved for the transformation of human mesenchymal cells into hematopoietic cells have demonstrated that cell fate can be dramatically altered by changing the epigenetic state of cells. Here, we demonstrate that umbilical cord-derived human mesenchymal stem cells (uMSC) are easily accessible and could be induced into cells with hematopoietic function. Furthermore, we focused on the crucial miRNAs and relative transcription factors (TFs) in our study. We show that combined Aza/GF incubation can increase expression of miR-218, miR-150, and miR-451. Accordingly, miR-218 overexpression achieved an increase in expression of CD34 (3-13%), CD45 (50-65%), CD133 and c-Kit in uMSCs that cultured with Aza/GF. The expression of the relevant transcriptional factors, such as HoxB4 and NF-Ya, was higher than in the negative control group or miR-218 inhibitor transfected group, and microphthalmia-associated transcription factor (MITF) is regarded to be a direct target of miR-218, as demonstrated by luciferase assays. Overexpression of miR-218 might, in conjunction with the MITF, upregulate the expression of NF-Ya and HoxB4, which induce a hematopoietic state. We concluded that miR-218 might have a role in the transformation of hematopoietic cells through the MITF pathway.
The dermal papilla (DP) cells in hair follicles function as critical regulators of hair growth. In particular, Alopecia Areata (AA) is closely related to the malfunctioning of the human dermal papilla cells(hDPCs). Thus, identifying the regulatory mechanism of hDPCs is important in inducing hair follicle (HFs) regeneration in AA patients. Recently, growing evidence indicated that 3’ untranslated regions (3’UTR) of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases though a so-called competing endogenous mechanism, but none has been reported in HFs regeneration. Here, we demonstrate that the 3’UTR of JAM-A could act as an essential competing endogenous RNA to maintain hDPCs function and promote HFs regeneration in AA. We showed that the 3’ UTR of junctional adhesion molecule A(JAM-A) shares many microRNAs(miRNAs) response elements, especially miR-221–3p, with versican(VCAN) mRNA, and JAM-A 3’UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs. Furthermore, upregulated VCAN can in turn promote the expression level of JAM-A. Overall, we propose that JAM-A 3’UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPCs maintenance, proliferation, and differentiation, which may lead to developing new therapies for hair loss.
Highlights: Cas9 RNA functions as a miRNA sponge. Let-7 is the dominant regulated miRNA by Cas9 RNA.RNA sequence optimization of Cas9 by synonymous mutation improves its safety.
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