Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin
| العنوان: | Mitochondrial transfer from mesenchymal stem cells to neural stem cells protects against the neurotoxic effects of cisplatin |
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| المؤلفون: | Gabriel S. Chiu, Cobi J. Heijnen, Nabila Boukelmoune, Annemieke Kavelaars |
| المصدر: | Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-13 (2018) Acta Neuropathologica Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone, Doublecortin Domain Proteins, Male, 0301 basic medicine, Mitochondrion, Hippocampal formation, lcsh:RC346-429, Mice, Neural Stem Cells, Enzyme Inhibitors, Cells, Cultured, reproductive and urinary physiology, Cerebral Cortex, Membrane Potential, Mitochondrial, Chemistry, Neural stem cell, Mitochondria, 3. Good health, Cell biology, medicine.anatomical_structure, Thiazolidines, biological phenomena, cell phenomena, and immunity, Microtubule-Associated Proteins, medicine.drug, Cholera Toxin, Doublecortin Protein, Wheat Germ Agglutinins, Neurotoxins, Subventricular zone, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, In vivo, medicine, Animals, Neuronal stem cells, Mitochondrial transfer, lcsh:Neurology. Diseases of the nervous system, Cisplatin, Research, Dentate gyrus, Neuropeptides, Mesenchymal stem cell, Bridged Bicyclo Compounds, Heterocyclic, nervous system diseases, Mice, Inbred C57BL, 030104 developmental biology, nervous system, Mesenchymal stem cells, Oligomycins, Neurology (clinical), Energy Metabolism |
| الوصف: | Mesenchymal stem cells (MSCs) transfer healthy mitochondria to damaged acceptor cells via actin-based intercellular structures. In this study, we tested the hypothesis that MSCs transfer mitochondria to neural stem cells (NSCs) to protect NSCs against the neurotoxic effects of cisplatin treatment. Our results show that MSCs donate mitochondria to NSCs damaged in vitro by cisplatin. Transfer of healthy MSC-derived mitochondria decreases cisplatin-induced NSC death. Moreover, mitochondrial transfer from MSCs to NSCs reverses the cisplatin-induced decrease in mitochondrial membrane potential. Blocking the formation of actin-based intercellular structures inhibited the transfer of mitochondria to NSCs and abrogated the positive effects of MSCs on NSC survival. Conversely, overexpression of the mitochondrial motor protein Rho-GTPase 1 (Miro1) in MSCs increased mitochondrial transfer and further improved survival of cisplatin-treated NSCs. In vivo, MSC administration prevented the loss of DCX+ neural progenitor cells in the subventricular zone and hippocampal dentate gyrus which occurs as a result of cisplatin treatment. We propose mitochondrial transfer as one of the mechanisms via which MSCs exert their therapeutic regenerative effects after cisplatin treatment. Electronic supplementary material The online version of this article (10.1186/s40478-018-0644-8) contains supplementary material, which is available to authorized users. |
| تدمد: | 2051-5960 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfeb87b44060415ba3b1c4ac9ec41fb3 https://doi.org/10.1186/s40478-018-0644-8 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cfeb87b44060415ba3b1c4ac9ec41fb3 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 20515960 |
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