miR-126-3p-loaded small extracellular vesicles secreted by urine-derived stem cells released from a phototriggered imine crosslink hydrogel could enhance vaginal epithelization after vaginoplasty
Abstract:Background
Due to the large area and deep width of the artificial neovagina after vaginoplasty, it takes a considerable amount of time to achieve complete epithelization of the neovagina. Currently, the clinical therapies for vaginal epithelization after vaginoplasty are still dissatisfactory. Recent studies showed that small extracellular vesicles (sEVs) derived from stem cells could accelerate wound epithelization. The sustained release of sEVs from optimized hydrogels may be a promising stra… Show more
“…al. recently demonstrated how EVs, derived from human urinederived stem cells and infused in hydrogel-based implants for in vivo rabbit vaginoplasty, induced signi cantly increased epithelialization and angiogenesis, and, furthermore, upregulated the intracellular ERK1/2 phosphorylation [24].…”
Section: Discussionmentioning
confidence: 99%
“…The cell migration and proliferation in wounded epithelial tissue is orchestrated by complex signaling pathways, and improved knowledge on these pathways could therefore enable further development of target-speci c wound healing treatments [21,22]. In previous animal models, extracellular vesicles (EVs) derived from mesenchymal stem cells have been associated with therapeutic effects regulating various phases of wound healing [23,24]. EVs are secreted by all cell types and consist of lipid bilayered structures originating from the cellular endosomal pathway.…”
Autologous micrografting is a technique currently applied within skin wound healing, however, the potential use for surgical correction of other organs with epithelial lining, including the urinary bladder, remains largely unexplored. Currently, little is known about the micrograft expansion potential and the micromolecular events that occur in micrografted urothelial cells. In this study, we aimed to evaluate the regenerative potential of different porcine urothelial micrograft sizes in vitro, and, furthermore, to explore how urothelial micrografts communicate and which microcellular events are triggered. We demonstrated that increased tissue fragmentation subsequently potentiated the yield of proliferative cells and the cellular expansion potential, which confirms, that the micrografting principles of skin epithelium also apply to uroepithelium. Furthermore, we targeted the expression of the extracellular signal-regulated kinase (ERK) pathway and demonstrated that ERK activation occurred predominately at the micrograft borders and that ERK inhibition led to decreased urothelial migration and proliferation. Finally, we successfully isolated extracellular vesicles from the micrograft culture medium and evaluated their contents and relevance within various enriched biological processes. Our findings substantiate the potential of applying urothelial micrografting in future tissue-engineering models for reconstructive urological surgery, and, furthermore, highlights certain mechanisms as potential targets for future wound healing treatments.
“…al. recently demonstrated how EVs, derived from human urinederived stem cells and infused in hydrogel-based implants for in vivo rabbit vaginoplasty, induced signi cantly increased epithelialization and angiogenesis, and, furthermore, upregulated the intracellular ERK1/2 phosphorylation [24].…”
Section: Discussionmentioning
confidence: 99%
“…The cell migration and proliferation in wounded epithelial tissue is orchestrated by complex signaling pathways, and improved knowledge on these pathways could therefore enable further development of target-speci c wound healing treatments [21,22]. In previous animal models, extracellular vesicles (EVs) derived from mesenchymal stem cells have been associated with therapeutic effects regulating various phases of wound healing [23,24]. EVs are secreted by all cell types and consist of lipid bilayered structures originating from the cellular endosomal pathway.…”
Autologous micrografting is a technique currently applied within skin wound healing, however, the potential use for surgical correction of other organs with epithelial lining, including the urinary bladder, remains largely unexplored. Currently, little is known about the micrograft expansion potential and the micromolecular events that occur in micrografted urothelial cells. In this study, we aimed to evaluate the regenerative potential of different porcine urothelial micrograft sizes in vitro, and, furthermore, to explore how urothelial micrografts communicate and which microcellular events are triggered. We demonstrated that increased tissue fragmentation subsequently potentiated the yield of proliferative cells and the cellular expansion potential, which confirms, that the micrografting principles of skin epithelium also apply to uroepithelium. Furthermore, we targeted the expression of the extracellular signal-regulated kinase (ERK) pathway and demonstrated that ERK activation occurred predominately at the micrograft borders and that ERK inhibition led to decreased urothelial migration and proliferation. Finally, we successfully isolated extracellular vesicles from the micrograft culture medium and evaluated their contents and relevance within various enriched biological processes. Our findings substantiate the potential of applying urothelial micrografting in future tissue-engineering models for reconstructive urological surgery, and, furthermore, highlights certain mechanisms as potential targets for future wound healing treatments.
“…They have multiple functions and also in uence tissue regeneration. Many researchers have investigated the functions of MSCs and MSCderived exosomes for vaginal tissue repair [30,31].The transplantation of UC-MSC can have multiple reparative bene ts, such as normal vaginal epithelial appearance, decreased brosis, and higher neovascularization [30]. In another study, exosomes derived from stem cells were shown to e ciently enhance angiogenesis and epithelization in rabbit vaginal mucosal defects [31].…”
Abstarct
Background
3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction.Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues.The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction.
Results
In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF).The biological scaffolds was constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated.It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue.Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats,which may through the PI3K/AKT signaling pathway.
Conclusions
Our results indicated that the 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.
“…Xu et al. [ 229 ] designed photo-triggered imine crosslinked hydrogels containing sEVs from human urinary-derived stem cells for the treatment of vaginal mucosal defects and observed epithelial formation and angiogenesis in the vaginal mucosal of rabbits. Fig.…”
Section: Tissue-specific Applications Of Ev-loaded Hydrogelsmentioning
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