Neuroprotective Effect of Bone Marrow–Derived Mononuclear Cells Promoting Functional Recovery from Spinal Cord Injury

2007 ◽  
Vol 24 (6) ◽  
pp. 1026-1036 ◽  
Author(s):  
Tomoyuki Yoshihara ◽  
Masayoshi Ohta ◽  
Yutaka Itokazu ◽  
Naoya Matsumoto ◽  
Mari Dezawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Mononuclear Cells ◽  
Neuroprotective Effect ◽  
Cord Injury

scholarly journals Comparison among bone marrow mesenchymal stem and mononuclear cells to promote functional recovery after spinal cord injury in rabbits

2017 ◽  
Vol 32 (12) ◽  
pp. 1026-1035
Author(s):  
Antônio Filipe Braga Fonseca ◽  
Jussara Peters Scheffer ◽  
Arthur Giraldi-Guimarães ◽  
Bárbara Paula Coelho ◽  
Raphael Mansur Medina ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Mononuclear Cells ◽  
Cord Injury

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background 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. Methods 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. Results 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. Conclusion 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.

scholarly journals B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1582 ◽  
Author(s):  
Takehiro Sugaya ◽  
Haruo Kanno ◽  
Michiharu Matsuda ◽  
Kyoichi Handa ◽  
Satoshi Tateda ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Tissue Damage ◽  
Neuroprotective Effect ◽  
Neural Tissue ◽  
Injured Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

scholarly journals CD157 mediates mitochondrial production and transfer from bone marrow mesenchymal stem cells (BMSCs) to improve neuronal apoptosis and functional recovery after spinal cord injury

2020 ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: 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. Methods: We modified BMSCs by CD-157, 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.Results: 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 and when objected to high concentration cADPR, ATP content and MMP of BMSCs also increased.Conclusion: This study evidences that CD157 can regulate the produce and transfer of BMSCs-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.

scholarly journals Two intrathecal transplants of bone marrow mononuclear cells produce motor improvement in an acute and severe model of spinal cord injury

2013 ◽  
Vol 12 (4) ◽  
pp. 274-277 ◽  
Author(s):  
Elisa Lettnin Kaminski ◽  
Asdrubal Falavigna ◽  
Gianina Terribele Venturin ◽  
Daniel Marinowic ◽  
Pamela Brambilla Bagatini ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Histological Analysis ◽  
Mononuclear Cells ◽  
Pcr Analysis ◽  
Bone Marrow Mononuclear Cells ◽  
Injury Site ◽  
Cord Injury

OBJECTIVE: We studied transplants of bone marrow mononuclear cells (BMMC) by lumbar puncture (LP) in a severe model of spinal cord injury (SCI) using clip compression. METHODS: BMMCs or saline solution were transplanted by LP 48 hours and 9 days post injury. Motor function was evaluated by BBB scale, histological analysis by Nissl technique and the verification of cell migration by PCR analysis. RESULTS: The BBB had significantly improved in rats treated with BMMCs by LP compared with controls (p<0.001). The histological analysis did not showed difference in the lesional area between the groups. The PCR analysis was able to found BMMCs in the injury site. CONCLUSIONS: two BMMC transplants by LP improved motor function in a severe model of SCI and BMMC was found in the injury site.

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