Dataset Information

MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing.

ABSTRACT: Adipose-derived stem cells (ADSCs) have been widely applied in translational and regenerative medicine. During aging, there is a recognized functional decline in ADSCs, which compromises their therapeutic effectiveness. Currently, the mechanisms of aging-induced stem cell dysfunction remain unclear, hence there is a need to elucidate these mechanisms and propose strategies for reversing this functional impairment. In this study, we found that ADSCs isolated from old donors (O-ADSCs) presented inferior phenotypes and decreased miR-145-5p levels compared to those from young donors (Y-ADSCs). To interrogate the role of miR-145-5p in ADSCs, gain- and loss-of-function assays were performed. The results indicated that miR-145-5p overexpression in O-ADSCs promoted cellular proliferation and migration, while reducing cell senescence. Further study demonstrated that miR-145-5p could regulate ADSCs function by targeting bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER), which is a crucial modulator in angiogenesis. Moreover, in vivo experiments showed that miR-145-5p-overexpressing O-ADSCs accelerated wound healing by promoting wound re-epithelialization and angiogenesis. Collectively, this study indicates that miR-145-5p works as a positive regulator for optimizing O-ADSCs function, and may be a novel therapeutic target for restoring aging-associated impairments in stem cell function.

SUBMITTER: Li C

PROVIDER: S-EPMC10903265 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing.

Li Chengcheng C Ren Sen S Xiong Hewei H Chen Jing J Jiang Tao T Guo Jiahe J Yan Chengqi C Chen Zhenbing Z Yang Xiaofan X Xu Xiang X

Biology open 20240219 2

Adipose-derived stem cells (ADSCs) have been widely applied in translational and regenerative medicine. During aging, there is a recognized functional decline in ADSCs, which compromises their therapeutic effectiveness. Currently, the mechanisms of aging-induced stem cell dysfunction remain unclear, hence there is a need to elucidate these mechanisms and propose strategies for reversing this functional impairment. In this study, we found that ADSCs isolated from old donors (O-ADSCs) presented in ...[more]

PMID: 38315073

Similar Datasets

Project description:BackgroundPersistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts (HDFs), partially leading to delayed skin wound healing. Extracellular vesicles (EVs) containing multiple pro-healing microRNAs (miRNAs) have been shown to exert therapeutic effects on diabetic wound healing. The present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells (P-MSC-EVs) on diabetic wound healing and high glucose (HG)-induced senescent fibroblasts and to explore the underlying mechanisms.MethodsP-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice, to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological analysis. Next, a series of assays were conducted to evaluate the effects of low (2.28 x 1010 particles/ml) and high (4.56 x 1010 particles/ml) concentrations of P-MSC-EVs on the senescence, proliferation, migration, and apoptosis of HG-induced senescent HDFs in vitro. Then, miRNA microarrays and real-time quantitative PCR (RT-qPCR) were carried out to detect the differentially expressed miRNAs in HDFs after EVs treatment. Specific RNA inhibitors, miRNA mimics, and small interfering RNA (siRNA) were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent HDFs.ResultsLocal injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths, with better-organized collagen deposition and decreased p16INK4a expression. In vitro, P-MSC-EVs enhanced the antisenescence, proliferation, migration, and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent manner. MiR-145-5p was found to be highly enriched in P-MSC-EVs. MiR-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent fibroblasts. MiR-145-5p mimics simulated the effects of P-MSC-EVs on functional improvements of fibroblasts by suppressing the expression of cyclin-dependent kinase inhibitor 1A and activating the extracellular signal regulated kinase (Erk)/protein kinase B (Akt) signaling pathway. Furthermore, local application of miR-145-5p agomir mimicked the effects of P-MSC-EVs on wound healing.ConclusionsThese results suggest that P-MSC-EVs accelerate diabetic wound healing by improving the function of senescent fibroblasts through the transfer of miR-145-5p, which targets cyclin-dependent kinase inhibitor 1A to activate the Erk/Akt signaling pathway. P-MSC-EVs are promising therapeutic candidates for diabetic wound treatment.

Project description:BackgroundSenescent adipose-derived stem cells (ASCs) exhibit reduced therapeutic efficacy during wound healing. Transcriptional regulation factors including long noncoding RNAs (lncRNAs) reportedly have essential roles in stem cell aging. However, the mechanisms of which lncRNAs influence mesenchymal stem cell aging and how it works need further investigation.MethodsThe expression patterns of lncRNA senescence-associated noncoding RNA (SAN) and miR-143-3p in ASCs obtained from old and young volunteer donors were detected by quantitative polymerase chain reaction. ASCs with overexpression or knockdown of SAN and γ-adducin (ADD3) were constructed by lentiviral transduction. Mimic and inhibitor were used to manipulate the cellular level of miR-143-3p in ASCs. The effects of these RNAs on ASCs proliferation, migration and cellular senescence were examined by EdU, transwell and senescence-activated β-galactosidase (SA-β-gal) staining assays. Wound scratch and tube formation assays were conducted to evaluate the capacities of ASCs in promoting fibroblasts migration and endothelial cells angiogenesis. Furthermore, dual-luciferase assays and rescue experiments were performed to identify the RNA interactions. Finally, the therapeutic effects of SAN-depleted aged ASCs were evaluated in a skin injury model.ResultsThe lncRNA SAN (NONHSAT035482.2) was upregulated in aged ASCs; it controlled cellular senescence in ASCs. lncRNA SAN knockdown in ASCs led to ASC functional enhancement and the inhibition of cellular senescence; it also promoted the effects of conditioned medium (CM) on endothelial cell tube formation and fibroblast migration. Mechanistic analysis showed that SAN serves as a sponge for miR-143-3p, thereby regulating the expression of ADD3. The application of SAN-depleted aged ASCs increased re-epithelialization, collagen deposition, neovascularization and led to accelerated skin wound closure, compared with transplantation of aged ASCs.ConclusionThe lncRNA SAN mediates ASC senescence by regulating the miR-143-3p/ADD3 pathway, providing a potential target for rejuvenation of senescent ASCs and enhancement of wound repair.

Dataset Information

MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing.

Publications

MiR-145-5p overexpression rejuvenates aged adipose stem cells and accelerates wound healing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets