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Bio-Pulsed Stimulation Effectively Improves the Production of Avian Mesenchymal Stem Cell-Derived Extracellular Vesicles That Enhance the Bioactivity of Skin Fibroblasts and Hair Follicle Cells

ABSTRACT: Mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) possess regeneration, cell proliferation, wound healing, and anti-senescence capabilities. The functions of exosomes can be modified by preconditioning MSCs through treatment with bio-pulsed reagents (Polygonum multiflorum Thunb extract). However, the beneficial effects of bio-pulsed small extracellular vesicles (sEVs) on the skin or hair remain unknown. This study investigated the in vitro mechanistic basis through which bio-pulsed sEVs enhance the bioactivity of the skin fibroblasts and hair follicle cells. Avian-derived MSCs (AMSCs) were isolated, characterized, and bio-pulsed to produce AMSC-sEVs, which were isolated, lyophilized, characterized, and analyzed. The effects of bio-pulsed AMSC-sEVs on cell proliferation, wound healing, and gene expression associated with skin and hair bioactivity were examined using human skin fibroblasts (HSFs) and follicle dermal papilla cells (HFDPCs). Bio-pulsed treatment significantly enhanced sEVs production by possibly upregulating RAB27A expression in AMSCs. Bio-pulsed AMSC-sEVs contained more exosomal proteins and RNAs than the control. Bio-pulsed AMSC-sEVs significantly augmented cell proliferation, wound healing, and gene expression in HSFs and HFDPCs. The present study investigated the role of bio-pulsed AMSC-sEVs in the bioactivity of the skin fibroblasts and hair follicle cells as mediators to offer potential health benefits for skin and hair.

SUBMITTER: Shieh J

PROVIDER: S-EPMC9740660 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Project description:Rationale: β-catenin signaling controls multiple fibroblast subsets, with its overactivity promoting the differentiation of hair follicle dermal stem cells (hfDSCs) and the hyperactivation of interfollicular fibroblasts. Understanding the concept of hfDSC activation and modulation offers hope towards the therapeutic armamentarium in dermatology and related comorbidities, as well as their potential applications in gerontology (the study of physiological aging). Having a comprehensive understanding in this stochastic process could also further yield important, novel insights into the molecular basis of skin aging to improve lifespan and preventing aging-related diseases. Methods: A new CD34CrePGR mouse line was generated. Through fate-tracing models and a series of β-catenin genetic experiments, our study depicts how the wound environment increases phosphorylated β-catenin in hfDSCs and facilitates their differentiation into dermal papilla (DP) and dermal sheath (DS). In mice carrying hfDSC-specific activated allele of β-catenin, hfDSCs accelerated their differentiation into DP cells. Results: Notably, with β-catenin stabilization in CD34-expressing cells and potential activation of canonical Wnt signaling, the mutant mice showed a brief increase of hair density in the short term, but over time leads to a senescence phenotype developing premature canities and thinning [hair follicle (HF) miniaturization]. Conclusion: β-catenin signaling drove HF senescence by accelerating differentiation of CD34+ hfDSCs, resulting in phenotypes attributable to the differentiation of the hfDSCs into DP cells and the loss of their stem cell potential. Therefore, our study reveals that the regulation of β-catenin signaling in hfDSCs may potentially become an important subject for future exploration in development of clinically effective therapies for hair loss treatment and an excellent model for revealing new therapeutic approaches to reverse aging or retarding the development of alopecia.

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Bio-Pulsed Stimulation Effectively Improves the Production of Avian Mesenchymal Stem Cell-Derived Extracellular Vesicles That Enhance the Bioactivity of Skin Fibroblasts and Hair Follicle Cells

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