Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING
Zixuan Sun, Tangrong Wang, Xiaomei Hou, Wenhuan Bai, Jiali Li, Yu Li, Jiaxin Zhang, Yuzhou Zheng, Zhijing Wu, Peipei Wu, Lirong Yan, Hui Qian
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引用次数: 0

Abstract

Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.

间充质基质细胞衍生的小细胞外囊泡通过调节孕区蛋白防止紫外线引起的光老化。
紫外线(UV)辐射是皮肤老化的主要外在因素,可导致皮肤光老化、光化性角化病(AK)甚至鳞状细胞癌(SCC)。目前,间充质基质细胞衍生的细胞外小泡(MSC-sEVs)在皮肤伤口愈合中的有益作用已被广泛报道,但在光老化领域仍有待探索。我们的研究结果表明,人脐带间充质干细胞衍生小泡(hucMSC-sEVs)干预可有效缓解体内和体外皮肤光老化表型,包括改善紫外线诱导的皮肤组织病理学变化,抑制氧化应激和真皮成纤维细胞(DFs)胶原降解。从机理上讲,使用 hucMSC-sEVs 预处理可逆转 UVA 诱导的真皮成纤维细胞妊娠区蛋白(PZP)下调,并通过抑制基质金属蛋白酶-1(MMP-1)表达和减少 DNA 损伤实现光保护。临床观察发现,AK 和 SCC 原位样本中的 PZP 明显减少,而侵袭性 SCC 样本中的 PZP 则出现反弹。总之,我们的研究结果揭示了hucMSC-sEVs在调节PZP以对抗光老化方面的有效作用,并为hucMSC-sEVs作为一种有效的皮肤光保护剂的潜在开发提供了新的临床前证据。
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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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