Enhancing hair regrowth using rapamycin-primed mesenchymal stem cell-derived exosomes.

IF 12.4 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-06-09 eCollection Date: 2025-01-01 DOI:10.7150/thno.107659
Manju Shrestha, Tiep Tien Nguyen, Rabyya Kausar, Dinesh Chaudhary, Ines Ferdiana Puspitasari, Hu-Lin Jiang, Hyung-Sik Kim, Simmyung Yook, Jee-Heon Jeong
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引用次数: 0

Abstract

Rationale: Hair loss affects millions globally, with limited effective treatments available and significant psychological impacts. Mesenchymal stem cells (MSCs) and MSC-derived exosomes hold therapeutic potential by modulating cellular communication, reducing inflammation, and supporting hair follicular regeneration. Rapamycin, a mechanistic target of rapamycin (mTOR) inhibitor, enhances MSC therapeutic potential by promoting the release of growth factors and signaling molecules. Thus, this study explores the benefit of priming effect of rapamycin on enhancing the function of MSC-derived exosomes to promote hair regrowth in a depilation-induced murine model. Methods: MSCs were primed with rapamycin, and exosomes were extracted from the MSC-conditioned media using ultrafiltration and poly (ethylene glycol) (PEG) precipitation. Dermal fibroblasts were treated with several doses of exosomes to evaluate the in vitro effect of rapamycin-primed MSC-derived exosomes (REXO). The depilated mice were administered exosomes via intradermal route and the hair regrowth was monitored for 15 days, followed by gene expression analysis and histological examination. Results: Dermal fibroblasts treated with REXO showed a higher proliferation rate and an increase in genes related to Wnt/β-catenin signaling, autophagy, and growth factors compared to non-primed MSC-derived exosomes (CEXO). In vivo REXO therapy via intradermal injection to the depilated areas in mice enhanced hair follicle development, hair density, and hair activation markers compared with the control and naive exosome treatments. Conclusion: REXO therapy effectively enhances hair regrowth thus this approach could offer a clinically effective therapy for hair loss treatment.

利用雷帕霉素引发的间充质干细胞衍生的外泌体促进头发再生。
理由:脱发影响着全球数百万人,有效的治疗方法有限,心理影响很大。间充质干细胞(MSCs)和MSCs衍生的外泌体通过调节细胞通讯、减少炎症和支持毛囊再生具有治疗潜力。雷帕霉素是雷帕霉素(mTOR)抑制剂的机制靶点,通过促进生长因子和信号分子的释放来增强MSC的治疗潜力。因此,本研究在脱毛诱导的小鼠模型中探讨了雷帕霉素的启动效应对增强msc来源的外泌体促进毛发再生的功能的益处。方法:用雷帕霉素引物MSCs,用超滤和聚乙二醇(PEG)沉淀法从MSCs条件培养基中提取外泌体。用几种剂量的外泌体处理真皮成纤维细胞,以评估雷帕霉素引发的msc衍生外泌体(REXO)的体外效果。脱毛小鼠经皮内注射外泌体,观察15 d后毛发再生情况,并进行基因表达分析和组织学检查。结果:与未引物的msc衍生外泌体(CEXO)相比,REXO处理的真皮成纤维细胞显示出更高的增殖率,Wnt/β-catenin信号、自噬和生长因子相关基因增加。与对照组和初始外泌体治疗相比,通过皮内注射REXO治疗小鼠脱毛区可增强毛囊发育、头发密度和头发激活标志物。结论:REXO疗法能有效促进毛发再生,为脱发治疗提供了一种临床有效的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
期刊介绍: Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.
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