Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima 10, 10-748, Olsztyn, Poland.
LaCell LLC, New Orleans, LA, USA.
Sci Rep. 2020 Nov 18;10(1):20035. doi: 10.1038/s41598-020-76796-7.
Human adipose-derived stem cells (ASCs) have potential to improve wound healing; however, their equivalents from domestic animals have received less attention as an alternative cell-based therapy for animals or even humans. Hypoxia is essential for maintaining stem cell functionality in tissue-specific niches. However, a cellular response to low oxygen levels has not been demonstrated in pig ASCs. Hence, the goal of our study was to characterize ASCs isolated from the subcutaneous fat of domestic pigs (pASCs) and examine the effect of hypoxia on their proteome and functional characteristics that might reproduce pASCs wound healing ability. Analysis of immunophenotypic and functional markers demonstrated that pASCs exhibited characteristics of mesenchymal stem cells. Proteomic analysis revealed 70 differentially abundant proteins between pASCs cultured under hypoxia (1% O) or normoxia (21% O). Among them, 42 proteins were enriched in the cells exposed to low oxygen, whereas 28 proteins showed decrease expression following hypoxia. Differentially expressed proteins were predominantly involved in cell metabolism, regulation of focal and intracellular communication, and attributed to wound healing. Functional examination of hypoxic pASCs demonstrated acquisition of contractile abilities in vitro. Overall, our results demonstrate that hypoxia pre-conditioning impacts the pASC proteome signature and contractile function in vitro and hence, they might be considered for further cell-based therapy study on wound healing.
人脂肪来源的干细胞 (ASCs) 具有改善伤口愈合的潜力;然而,作为动物甚至人类的替代细胞疗法,其同源物来自家畜的情况较少受到关注。缺氧对于维持组织特异性龛位中的干细胞功能至关重要。然而,猪 ASC 对低氧水平的细胞反应尚未得到证明。因此,我们的研究目的是表征从家猪皮下脂肪中分离的 ASC(pASC),并研究低氧对其蛋白质组和功能特性的影响,这些特性可能再现 pASC 的伤口愈合能力。免疫表型和功能标志物分析表明,pASC 表现出间充质干细胞的特征。蛋白质组学分析显示,在低氧(1% O)或常氧(21% O)培养条件下的 pASC 之间有 70 个差异丰度蛋白。其中,42 种蛋白在低氧暴露的细胞中富集,而 28 种蛋白在低氧后表达减少。差异表达的蛋白主要参与细胞代谢、局灶和细胞内通讯的调节,并与伤口愈合有关。低氧 pASC 的功能检测显示其在体外获得了收缩能力。总体而言,我们的研究结果表明,低氧预处理会影响 pASC 的蛋白质组特征和体外收缩功能,因此,它们可能被考虑用于进一步的伤口愈合细胞治疗研究。