Background Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing. Methods hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis. Results Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha. Conclusion Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.
Background: Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originated from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing.Methods: hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis.Results: PF-127/hADSCs-Exos complex enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), reduced inflammation (IL-6, TNF-α, CD68, CD206), and up-regulated expression of skin barrier proteins (KRT1, AQP3). The results showed that both PF-127/hADSCs-Exos and hADSCs-Exos could improve the cwound healing process at a similar level.Conclusion: PF-127/hADSCs-Exos combination can maintain the bioactivity of hADSCs-Exos and control the exosome release. The low-frequency administration of PF-127/hADSCs-Exos could promote cutaneous wound healing instead of the high-frequency administration of pure exosomes. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds.
Background: Human adipose tissue-derived stem cells (hADSCs) are considered an ideal source of cells for regenerative medicine. Mesenchymal stem cells derived-exosomes (MSC-Exos) are being opined as new cell-free therapeutics for numerous human diseases. For future clinical applications, the safety of allogenic hADSCs and hADSCs-derived exosomes (hADSCs-Exos) needs to be addressed and verified in pre-clinical animal models. This study sought to evaluate the toxicity of hADSCs and hADSCs-Exos by performing in vivo and in vitro toxicological assessments.Methods: We used IVIS to track the biodistribution of GFP-labeled hADSCs and the PKH26-labeled in a mouse model. The tumorigenicity of hADSCs and hADSCs-Exos was analyzed by soft agar colony formation assay and nude mice tumorigenicity test in vitro and in vivo. The acute animal toxicity and allergenicity test were used to explore the toxicological profile of hADSCs and hADSCs-Exos in mice.Results: We found that hADSCs-Exos accumulated faster in the tissues of mice and were also cleared more rapidly compared to hADSCs. Both hADSCs and hADSCs-Exos have little risk of tumorigenicity, and hADSCs-Exos had lower toxicity and lower immunogenicity than hADSCs.Conclusion: Our study is the first to compare the safety between hADSCs and hADSCs-Exos, and revealed that hADSCs-Exos are safer for application as systemic therapy, without complications in toxicological assessment, and have a better prospective utility as a treatment agent and for drug delivery.
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