Wound healing effect of adipose-derived stem cells: A critical role of secretory factors on human dermal fibroblasts
Won-Serk Kim, Byung-Soon Park, Jong-Hyuk Sung, Jun-Mo Yang, Seok-Beom Park, Sahng-June Kwak, Jeong-Soo Park
Summary
Background: Adipose-derived stem cells (ADSCs) are a population of pluripotent cells, which have characteristics similar to bone marrow-derived mesenchymal stem cells. Whereas ADSCs have potential applications for the repair and regeneration of various damaged tissues, few studies have dealt with the effect of ADSCs on fibroblasts, which play a key role in skin biology.
Objective: In this study, we investigated the possible roles of ADSCs in skin wound healing process, especially in the aspect of fibroblast activation–—proliferation, collagen synthesis and migratory properties.
Methods and results: ADSCs promoted human dermal fibroblast (HDF) proliferation, not only by cell-to-cell direct contact, which was confirmed by co-culture experiment, but also by paracrine activation through secretory factors, resolved by transwell co-culture and culturing with conditioned medium of ADSCs (ADSC-CM). ADSC-CM enhanced the secretion of type I collagen in HDFs by regulating the mRNA levels of extracellular matrix (ECM) proteins: up-regulation of collagen type I, III and fibronectin and down-regulation of MMP-1. Moreover, ADSC-CM showed stimulatory effect on migration of HDFs in in vitro wound healing models. Additional to those in vitro evidences, wound healing effect of ADSCs was also verified with in vivo animal study, resulted that ADSCs significantly reduced the wound size and accelerated the re-epithelialization from the edge.
Conclusion: Collectively, these data suggest that ADSC is constitutionally well suited for dermal wound healing and secretory factors derived from ADSCs promote wound healing via HDFs and ADSCs can be used for the treatment of photoaging and wound healing.
脂肪源性干细胞对创面愈合的影响:一个分泌因子对人真皮成纤维细胞产生影响重要的角色
总结
背景:脂肪源性干细胞(ADSCs)与骨髓间充质干细胞许多特征相似,是一种多潜能细胞。ADSCs具有修复和再生损坏的组织的应用潜能,但是对于ADSCs对皮肤生物学中起关键作用的成纤维细胞的影响研究却很少。
目的:本研究是观察ADSCs在皮肤创面愈合过程中的可能作用,特别是观察ADSCs在对成纤维细胞的增殖活性、合成胶原和迁移特性方面的影响。
方法和结果:ADSCs促进人真皮成纤维细胞(HDF)的增殖,不仅是通过细胞与细胞的直接作用(共培养实验),而且通过细胞因子的旁分泌作用(通过半透膜的共培养和ADSCs的条件培养液)。ADSCs的条件培养液通过调节HDF的细胞外基质蛋白的mRNA水平来促进Ⅰ型胶原的分泌:上调Ⅰ、Ⅲ型胶原和纤维连接素,下调MMP-1。而且,ADSCs条件培养液在体外创面模型中对HDFs的迁移有促进作用。除了体外证据,ADSCs的创面愈合作用在动物体内也被证明,ADSCs可以显著减小创面的大小和加速创面边缘的再上皮化。
结论:综合所有的结果,ADSC非常有助于创面愈合,同时ADSC分泌的因子可以通过对真皮成纤维细胞的影响来加速创面愈合,所以ADSCs可以被用于治疗皮肤衰老和创面愈合。