Exosomes from antler stem cells alleviates MSC senescence and osteoarthritis

The therapeutic functions of stem cells were mainly depending on paracrine effects rather than their own proliferation and differentiation on site. In advantage of easy to collected from conditioned medium, have contents of cytokines, growth factors, signaling lipids, mRNAs, and regulatory miRNAs, exosomes from stem cells were considered to be a promising material for stem cell-based cell-free therapies. In traditional Chinese medicine, antler extracts have been used to alleviates aging and aging related diseases. We have demonstrated that exosomes from antler stem cells (ASCs), the source of the annual full regeneration of deer antler, could alleviate cellular senescence and aging related diseases. With exosomes treatment, the senescent phenotype of primary MSCs and hMSCs at late passage were significantly mitigated. When injected into articular cavity, exosomes from ASCs markedly promote joint function recovery and bone and cartilage regeneration. By LC-MS/MS assay, we found that exosomes from ASCs contain various proteins which in the regulation of biological processes including cell proliferation and migration, immunoregulation, wound healing and angiogenesis. With the advantages of abundant sources, low risk of tumorigenicity and immunogenicity, exosomes from ASCs may consider as a promising bio-material for cell-free therapies in the future. Overall design: In mice, PBS-treated controls, osteoarthritis modeling, and exosomes-treated mice joint. Among hMSCs, PBS-treated control and exosome-treated cells. Among primary MSCs, PBS-treated control and exosome-treated cells.

干细胞的治疗功能主要依赖于旁分泌效应，而非其在原位的增殖与分化。干细胞来源的外泌体（exosomes）可从条件培养基中便捷获取，且富含细胞因子、生长因子、信号脂质、mRNA及调控性miRNA，因此被视为基于干细胞的无细胞治疗领域极具前景的材料。
在传统中医药领域，鹿茸提取物已被用于缓解衰老及衰老相关疾病。我们的研究证实，作为鹿茸年度完全再生来源的鹿茸干细胞（antler stem cells, ASCs）所分泌的外泌体，能够有效缓解细胞衰老及衰老相关疾病。经外泌体处理后，晚期传代的原代间充质干细胞（mesenchymal stem cells, MSCs）与人源间充质干细胞（human mesenchymal stem cells, hMSCs）的衰老表型得到显著缓解。
当将外泌体注入关节腔后，鹿茸干细胞来源的外泌体可显著促进关节功能恢复以及骨与软骨再生。通过液相色谱-串联质谱（LC-MS/MS）分析，我们发现鹿茸干细胞来源的外泌体含有多种蛋白质，这些蛋白质参与调控细胞增殖与迁移、免疫调节、伤口愈合及血管生成等多种生物学过程。
鹿茸干细胞来源的外泌体具有来源丰富、致瘤性与免疫原性低等显著优势，有望在未来成为无细胞治疗的优质生物材料。
整体实验设计如下：小鼠模型分组包括PBS处理对照组、骨关节炎造模组与外泌体处理组小鼠关节；人源间充质干细胞实验组设置PBS处理对照组与外泌体处理组细胞；原代间充质干细胞实验组设置PBS处理对照组与外泌体处理组细胞。