Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord.
Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord.
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DOI：
10.1371/journal.pone.0190358
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kocsis JD
中科院分区：
文献类型：
--
作者：
Lankford KL;Arroyo EJ;Nazimek K;Bryniarski K;Askenase PW;Kocsis JD
在之前的一篇报道中，我们发现静脉输注骨髓间充质干细胞(MSCs)可以改善非免疫抑制大鼠脊髓挫伤(SCI)后的功能恢复，尽管在脊髓损伤(SCI)部位没有检测到MSCs。相反，骨髓间充质干细胞在输液后短暂停留在肺部约两天。初步研究和最近的一份报告表明，静脉(IV)输注MSCs的效果可以通过静脉输注从MSC培养条件培养液中分离出来的外切体(MSCexos)来模拟。本研究通过观察大鼠脊髓损伤后3小时和24小时静脉注射DIR荧光标记MSCexos的组织分布和细胞靶向性，探讨MSCexos抗脊髓损伤的可能机制。静脉注射的MSCexos在脊髓挫伤区域检测到，但在脊髓非损伤区域检测不到，在脾中也检测到，与对照组相比，SCI大鼠的体重显著减轻。DIR“热点”与脊髓中表达CD206的M2巨噬细胞特异性相关，这一点通过与抗CD63抗体共同定位而得到证实，该抗体标记了一个典型地表达在外体上的Tetraspanin。我们的发现MSCexos特异性靶向脊髓损伤部位的M2型巨噬细胞，支持MSCs释放的细胞外小泡可能至少介导了静脉注射MSC的部分治疗效果的观点。
In a previous report we showed that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) improved functional recovery after contusive spinal cord injury (SCI) in the non-immunosuppressed rat, although the MSCs themselves were not detected at the spinal cord injury (SCI) site. Rather, the MSCs lodged transiently in the lungs for about two days post-infusion. Preliminary studies and a recent report suggest that the effects of intravenous (IV) infusion of MSCs could be mimicked by IV infusion of exosomes isolated from conditioned media of MSC cultures (MSCexos). In this study, we assessed the possible mechanism of MSCexos action on SCI by investigating the tissue distribution and cellular targeting of DiR fluorescent labeled MSCexos at 3 hours and 24 hours after IV infusion in rats with SCI. The IV delivered MSCexos were detected in contused regions of the spinal cord, but not in the noninjured region of the spinal cord, and were also detected in the spleen, which was notably reduced in weight in the SCI rat, compared to control animals. DiR “hotspots” were specifically associated with CD206-expressing M2 macrophages in the spinal cord and this was confirmed by co-localization with anti-CD63 antibodies labeling a tetraspanin characteristically expressed on exosomes. Our findings that MSCexos specifically target M2-type macrophages at the site of SCI, support the idea that extracellular vesicles, released by MSCs, may mediate at least some of the therapeutic effects of IV MSC administration.
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