Multipotent stromal cells stimulate skin regeneration after acute or chronic injuries. However, many stem cell therapy protocols are limited by the elevated number of cells required and poor cell survival after transplantation. Considering that the beneficial effects of multipotent stromal cells on wound healing are typically mediated by paracrine mechanisms, we examined whether the conditioned medium from skin-derived multipotent stromal cells would be beneficial for restoring the skin structure of mice after wounding. A proteomic characterization of skin-derived multipotent stromal cell-conditioned medium was performed, and the angiogenic function of this secretome was investigated in vitro using an endothelial cell tube formation assay. We then applied the skin-derived multipotent stromal cell-conditioned medium directly to full-thickness excisional wounds or embedded it into carrageenan or poly(vinyl alcohol) hydrogels to monitor tissue regeneration in mice. Biological processes related to wound healing and angiogenesis were highlighted by the analysis of the skin-derived multipotent stromal cell secretome, and a pro-angiogenic capacity for promoting tubule-like structures was first confirmed in vitro. Skin wounds treated with skin-derived multipotent stromal cell-conditioned medium also displayed increased angiogenesis, independently of the association of the conditioned medium with hydrogels. However, improvements in wound closure and epidermis or decreased inflammatory cell presence were not observed. Hence, the use of the secretome obtained from human skin-derived multipotent stromal cells may be a potential strategy to aid the natural skin repair of full-thickness lesions mainly based on its pro-angiogenic properties.

中文翻译：

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来自人皮肤的多能基质细胞促血管生成分泌蛋白组的皮肤再生潜力。

在急性或慢性损伤后，多能基质细胞刺激皮肤再生。但是，许多干细胞治疗方案受到所需细胞数量增加和移植后细胞存活率低的限制。考虑到多能干基质细胞对伤口愈合的有益作用通常是由旁分泌机制介导的，我们检查了来自皮肤的多能干基质细胞的条件培养基是否对恢复小鼠受伤后的皮肤结构有益。进行了皮肤来源的多能基质细胞条件培养基的蛋白质组学表征，并使用内皮细胞管形成试验在体外研究了该分泌蛋白的血管生成功能。然后，我们将源自皮肤的多能基质细胞条件培养基直接应用于全层切除伤口，或将其嵌入角叉菜胶或聚乙烯醇水凝胶中，以监测小鼠的组织再生。通过对皮肤衍生的多能基质细胞分泌组的分析突出了与伤口愈合和血管生成有关的生物学过程，并首次在体外确认了促进小管样结构的促血管生成能力。用皮肤衍生的多能基质细胞条件培养基处理的皮肤伤口也显示出增加的血管生成，独立于条件培养基与水凝胶的缔合。然而，未观察到伤口闭合和表皮改善或炎性细胞减少。因此，