Small extracellular vesicles secreted by urine-derived stem cells enhanced wound healing in aged mice by ameliorating cellular senescence
Small extracellular vesicles secreted by urine-derived stem cells enhanced wound healing in aged mice by ameliorating cellular senescence
复制标题
尿液干细胞分泌的小细胞外囊泡通过改善细胞衰老来增强老年小鼠的伤口愈合
DOI：
10.1016/j.jmst.2020.03.014
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发表时间：
2021-01-15
影响因子：
10.9
通讯作者：
Wang, Yang
中科院分区：
文献类型：
--
作者：
Sun, Yongjin;Zhang, Juntao;Wang, Yang
慢性皮肤伤口的组织再生仍然是再生医学的一个关键挑战，因为衰老细胞的积累和伤口部位衰老相关分泌表型（sasp）的分泌增加。最近，一些研究报道了来自干细胞的小细胞外囊泡（sev）可以缓解细胞衰老，并且发生肿瘤和免疫反应的风险非常低。我们之前的研究表明，尿源性干细胞（USCs）可以很容易且无创地获得，并且USCs衍生的sev （usc - sev）具有再生组织损伤的能力，因此利用usc - sev促进衰老组织的慢性皮肤伤口愈合可能是一种可行且有效的策略。因此，在本研究中，收集usc - sev，首先将其装载在人脱细胞羊膜（HAAM）中，以控制usc - sev在伤口部位的释放和定位，然后将其植入老年小鼠的慢性皮肤伤口。体内实验结果表明，HAAM中的usc - sev可以通过改善细胞衰老，减少老化皮肤创面中SASP的分泌，有效促进创面愈合。为了阐明其机制，我们利用usc - sev体外培养人真皮成纤维细胞（HDFs），结果表明usc - sev激活Sirtl通路后，通过逆转衰老HDFs的衰老表型和有效减少SASP的分泌，可以使衰老的成纤维细胞恢复活力。因此，usc - sev通过改善细胞衰老，有效促进老年小鼠伤口愈合。(C) 2020由爱思唯尔有限公司代表《材料科学与技术杂志》编辑部出版。
Regeneration of chronic skin wounds in tissue is still a key challenge in regenerative medicine because of the accumulation of senescent cells and increasing secretion of senescence-associated secretory phenotype4SASP) in the wound site. Recently, some studies have reported that small extracellular vesicles (sEVs) derived from stem cells can alleviate cellular senescence with very low risk of tumorigenesis and immune responses. As our previous studies have shown that urine-derived stem cells (USCs) can be obtained easily and noninvasively and sEVs derived from USCs (USC-sEVs) have capabilities of regenerating tissue injuries, using USC-sEVs to enhance chronic skin wound healing in aged tissue might be a feasible and efficient strategy. Therefore, in this study, the USC-sEVs were collected and firstly loaded in a human acellular amniotic membrane (HAAM) for controlled releasing and locating the USC-sEVs in the wound site before they were implanted into a chronic skin wound in aged mice. In vivo results showed that the USC-sEVs in HAAM could effectively accelerate the wound healing by ameliorating cellular senescence and reducing the secretion of SASP in the aged skin wounds. To elucidate the mechanism, USC-sEVs were used to in vitro culture human dermal fibroblasts (HDFs) and results showed that USC-sEVs could rejuvenate senescent fibroblasts by reversing the aging phenotypes of senescent HDFs and efficiently reducing the secretion of SASP after they activated the Sirtl pathway. Therefore, USC-sEVs are efficient for enhancing wound healing in aged mice by ameliorating cellular senescence. (C) 2020 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.