Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages.
Apoptotic bodies derived from mesenchymal stem cells promote cutaneous wound healing via regulating the functions of macrophages.
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间充质干细胞衍生的凋亡小体通过调节巨噬细胞的功能促进皮肤伤口愈合。
DOI：
10.1186/s13287-020-02014-w
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发表时间：
2020-11-27
影响因子：
7.5
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Liu J;Qiu X;Lv Y;Zheng C;Dong Y;Dou G;Zhu B;Liu A;Wang W;Zhou J;Liu S;Liu S;Gao B;Jin Y
作为机体与外界环境的主要界面，皮肤容易遭受各种损伤。皮肤损伤常常导致严重的残疾，探索有前景的治疗策略至关重要。基于外源性间充质干细胞（MSC）的疗法由于其明显的治疗效果是一种潜在的策略，然而其潜在机制仍不明确。有趣的是，我们在小鼠皮肤伤口愈合模型中观察到外源性骨髓间充质干细胞（BMMSC）在移植后的短时间内大量凋亡。考虑到细胞外囊泡（EV）在细胞间通讯中的作用，我们假设凋亡过程中释放的大量凋亡小体（AB）可能部分有助于治疗效果。
提取、鉴定了源自间充质干细胞的凋亡小体，并将其应用于小鼠皮肤伤口愈合模型，评估了其治疗效果。然后，探究了凋亡小体的靶细胞，并在体外研究了凋亡小体对巨噬细胞的影响。
我们发现源自间充质干细胞的凋亡小体通过促使巨噬细胞向M2表型极化促进了皮肤伤口愈合。此外，功能发生转变的巨噬细胞进一步增强了成纤维细胞的迁移和增殖能力，这些共同促进了伤口愈合过程。
总体而言，我们的研究表明，移植的间充质干细胞部分通过释放凋亡小体促进皮肤伤口愈合，这些凋亡小体能够使巨噬细胞转变为抗炎表型，在组织修复过程中发挥关键作用。
在线版本包含补充材料，可在10.1186/s13287 - 020 - 02014 - w获取。
As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process. The online version contains supplementary material available at 10.1186/s13287-020-02014-w.
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DOI：
10.1098/rstb.2017.0003
发表时间：
2018-01-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Gregory CD;Paterson M
通讯作者：
Paterson M
DOI：
10.1164/rccm.201701-0170oc
发表时间：
2017-11-15
影响因子：
24.7
作者：
Morrison, Thomas J.;Jackson, Megan V.;Krasnodembskaya, Anna D.
通讯作者：
Krasnodembskaya, Anna D.
影响因子：
16.6
作者：
Brock, Courtney K.;Wallin, Stephen T.;Eisenhoffer, George T.
通讯作者：
Eisenhoffer, George T.
影响因子：
7.5
作者：
Lee DE;Ayoub N;Agrawal DK
通讯作者：
Agrawal DK
影响因子：
29.4
作者：
Rani, Sweta;Ritter, Thomas
通讯作者：
Ritter, Thomas