Dataset Information

CD73⁺ adipose-derived stem cells reduce scar formation through PLOD1.

ABSTRACT:

Background

Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely through modulating macrophage polarization. In the present study, we tested whether a CD73⁺ subpopulation of AMSCs could reduce scar formation compared with CD73^- AMSCs.

Methods

The gene profile of CD73⁺ versus CD73^- AMSCs was obtained from a validated public database, GSE167219. AMSCs were isolated from adipose tissue surrounding the groin of mice, after which CD73⁺ versus CD73^- AMSCs were sorted using flow cytometry. PLOD1 levels were determined in CD73⁺ versus CD73^- AMSCs. Then, PLOD1 in CD73^- AMSCs was depleted by a short-hair interfering RNA against PLOD1 (sh-PLOD1), while PLOD1 in CD73⁺ AMSCs was increased by expression of a PLOD1 transgene. A blade was used to induce a skin injury on the middle back of the mice. Either CD73⁺ AMSCs or CD73⁺ PLOD1 AMSCs or CD73^- AMSCs or CD73^- sh-PLOD1 AMSCs were intravenously transplanted into the injured region of the mice. Fibrosis and the underlying mechanisms were investigated. Co-immunoprecipitation was performed to evaluate interaction between CD73 and PLOD1.

Results

CD73⁺ AMSCs expressed significantly lower levels of PLOD1, a potent stimulator of fibrosis, compared with CD73^- AMSCs. Transplantation of CD73⁺ AMSCs generated significantly reduced fibrosis at the skin injury site compared with CD73^- AMSCs. However, expression of PLOD1 in CD73⁺ AMSCs abolished its advantageous effects on fibrosis reduction, while depletion of PLOD1 in CD73^- AMSCs improved the outcome of fibrosis to the levels of transplantation of CD73⁺ AMSCs. Co-immunoprecipitation showed no direct protein interaction between CD73 and PLOD1.

Conclusions

CD73⁺ AMSCs are a subgroup of AMSCs with better therapeutic effects on wound healing, and can inhibit scar formation through reduced PLOD1 in an indirect manner.

SUBMITTER: Xu M

PROVIDER: S-EPMC8848413 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

CD73<sup>+</sup> adipose-derived stem cells reduce scar formation through PLOD1.

Xu Miao M Fang Shuo S Ma Xiaorong X

Annals of translational medicine 20220101 2

<h4>Background</h4>Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely t ...[more]

PMID: 35282129

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Project description:Hypertrophic scars, which result from aberrant fibrosis and disorganized collagen synthesis by skin fibroblasts, emerge due to disrupted wound healing processes. These scars present significant psychosocial and functional challenges to affected individuals. The current treatment limitations largely arise from an incomplete understanding of the underlying mechanisms of hypertrophic scar development. Recent studies, however, have shed light on the potential of exosomal non-coding RNAs interventions to mitigate hypertrophic scar proliferation. This research assesses the impact of exosomes derived from adipose-derived stem cells (ADSCs-Exos) on hypertrophic scar formation using a rabbit ear model. We employed Hematoxylin and Eosin staining, Masson’s Trichrome staining, and Immunohistochemical staining techniques to track scar progression. Our comprehensive analysis encompassed the differential expression of non-coding RNAs, enrichment analyses of functional pathways, protein-protein interaction studies, and miRNA-mRNA interaction investigations. The results reveal a marked alteration in the expression levels of long non-coding RNAs and microRNAs following ADSCs-Exos treatment, with little changes observed in circular RNAs. Notably, miR-194 emerges as a critical regulator within the signaling pathways that govern hypertrophic scar formation. Dual-luciferase assays indicated a significant reduction in the promoter activity of TGF-β1 after miR-194 overexpression. Quantitative reverse transcription PCR and Western blotting assays further validated the decrease in TGF-β1 expression in the treated samples. Moreover, the treatment resulted in diminished levels of inflammatory markers IL-1β, TNF-α, and IL-10. In vivo evidence strongly supports the role of miR-194 in attenuating hypertrophic scar formation through the suppression of TGF-β1. Our findings endorse the strategic use of ADSCs-Exos, particularly through miR-194 modulation, as an effective strategy for reducing scar formation and lowering pro-inflammatory and fibrotic indicators like TGF-β1. Therefore, this study advocates for the targeted application of ADSCs-Exos, with an emphasis on miR-194 modulation, as a promising approach to managing proliferative scarring.

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Dataset Information

CD73⁺ adipose-derived stem cells reduce scar formation through PLOD1.

Background

Methods

Results

Conclusions

Publications

CD73<sup>+</sup> adipose-derived stem cells reduce scar formation through PLOD1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

CD73+ adipose-derived stem cells reduce scar formation through PLOD1.

Background

Methods

Results

Conclusions

Publications

CD73<sup>+</sup> adipose-derived stem cells reduce scar formation through PLOD1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

CD73⁺ adipose-derived stem cells reduce scar formation through PLOD1.