Department of Biological Function of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
Department of Plant Physiology, Genetics, and Biotechnology, Faculty of Biology and Biotechnology, University of Warmia and Mazury, 10-719 Olsztyn, Poland.
Int J Mol Sci. 2021 May 22;22(11):5469. doi: 10.3390/ijms22115469.
The primary mechanism by which adipose-derived stem cells (ASCs) exert their reparative or regenerative potential relies predominantly on paracrine action. Secretory abilities of ASCs have been found to be amplified by hypoxia pre-conditioning. This study investigates the impact of hypoxia (1% O) on the secretome composition of pig ASCs (pASCs) and explores the effect of pASCs' conditioned media (CM) on skin cell functions in vitro and the expression of markers attributed to wound healing. Exposure of pASCs to hypoxia increased levels of vascular endothelial growth factor (VEGF) in CM-Hyp compared to CM collected from the cells cultured in normoxia (CM-Nor). CM-Hyp promoted the migratory ability of pig keratinocytes (pKERs) and delayed migration of pig dermal fibroblasts (pDFs). Exposure of pKERs to either CM-Nor or CM-Hyp decreased the levels of pro-fibrotic indicators and . Furthermore, CM-Hyp enhanced the expression of , the marker of the basal epidermis layer. In contrast, CM-Nor showed a stronger effect on pDFs manifested by increases in , , , and mRNA expression. The formation of three-dimensional endothelial cell networks was improved in the presence of CM-Hyp. Overall, our results demonstrate that the paracrine activity of pASCs affects skin cells, and this property might be used to modulate wound healing.
脂肪来源干细胞（ASCs）发挥其修复或再生潜能的主要机制主要依赖于旁分泌作用。已经发现，ASCs 的分泌能力通过低氧预处理得到放大。本研究调查了低氧（1% O）对猪 ASCs（pASCs）分泌组组成的影响，并探讨了 pASCs 条件培养基（CM）对体外皮肤细胞功能以及与伤口愈合相关标志物表达的影响。与在常氧（CM-Nor）中培养的细胞收集的 CM 相比，pASC 暴露于低氧（CM-Hyp）中增加了 CM 中的血管内皮生长因子（VEGF）水平。CM-Hyp 促进了猪角质形成细胞（pKERs）的迁移能力，并延迟了猪真皮成纤维细胞（pDFs）的迁移。pKERs 暴露于 CM-Nor 或 CM-Hyp 均可降低促纤维化标志物和的水平。此外，CM-Hyp 增强了基底表皮层标志物的表达。相比之下，CM-Nor 对 pDFs 的影响更强，表现为、、、和的 mRNA 表达增加。存在 CM-Hyp 时，内皮细胞网络的形成得到改善。总的来说，我们的结果表明 pASCs 的旁分泌活性影响皮肤细胞，并且这种特性可用于调节伤口愈合。
