CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury.
CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury.
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骨髓间充质干细胞中的CD157介导线粒体产生和转移，改善脊髓损伤后神经元凋亡和功能恢复
DOI：
10.1186/s13287-021-02305-w
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发表时间：
2021-05-17
影响因子：
7.5
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Li J;Li H;Cai S;Bai S;Cai H;Zhang X
近年来的研究表明，骨髓间充质干细胞（BMSCs）来源的自体线粒体可能在脊髓损伤（SCI）的治疗中具有重要价值。然而，线粒体从骨髓间充质干细胞转移到损伤的神经元的机制还不完全清楚。我们用细胞表面分子CD 157修饰骨髓间充质干细胞，作为线粒体转运的潜在调节剂，移植到脊髓损伤大鼠体内，与OGD损伤的VSC4.1运动神经元共培养。透射电镜观察细胞外线粒体颗粒，免疫组化和Western blotting检测CD 157/cyclic ADP-ribose信号通路相关蛋白的表达。用CD 157 ADP环化酶和Fluo-4 AM检测细胞内Ca 2+信号。所有数据均表示为平均值± SEM。通过GraphPad Prism 6软件进行统计学分析。两组间比较采用非配对t检验。通过单因素方差分析或双因素方差分析评价多重比较。当与损伤的VSC4.1运动神经元共培养时，BMSCs上的CD 157上调。上调BMSCs表面CD 157表达可增加细胞外线粒体颗粒向VSC4.1运动神经元的转移，使VSC4.1运动神经元轴突逐渐再生，减少细胞凋亡。将CD 157修饰的骨髓间充质干细胞移植于脊髓损伤大鼠的损伤部位，可明显促进脊髓损伤大鼠的功能恢复、轴突再生和神经元凋亡。在高浓度cADPR刺激下，CD 157修饰的BMSCs细胞内Ca 2+水平明显升高，ATP含量和MMP含量也明显增加。本研究结果提示，CD 157可以调控骨髓基质细胞来源的细胞外线粒体颗粒的产生和转移，丰富了骨髓基质细胞移植中细胞外线粒体转移的机制，为改善干细胞治疗脊髓损伤提供了新的策略。
Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.
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DOI：
10.1093/brain/aww039
发表时间：
2016-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Bartus K;Galino J;James ND;Hernandez-Miranda LR;Dawes JM;Fricker FR;Garratt AN;McMahon SB;Ramer MS;Birchmeier C;Bennett DL;Bradbury EJ
通讯作者：
Bradbury EJ
影响因子：
4.2
作者：
Baptiste, DC;Fehlings, MG
通讯作者：
Fehlings, MG
影响因子：
4.8
作者：
Rah, SY;Park, KH;Kim, UH
通讯作者：
Kim, UH
影响因子：
5.3
作者：
Patterson, Thomas E.;Boehm, Cynthia;Muschler, George F.
通讯作者：
Muschler, George F.
影响因子：
4.7
作者：
DiSabato DJ;Quan N;Godbout JP
通讯作者：
Godbout JP