Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210
DOI:
https://doi.org/10.22317/jcms.v6i3.781Abstract
Objective: In this study, we evaluated the effects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration.
Methods: The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCsGFP) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining.
Results: Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 significantly upregulated in both brain and blood samples.
Conclusion: According to the findings, hESC-NPCsGFP injection could up-regulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative effect of hESC-NPCsGFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region.
References
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35. Willis CM, Nicaise AM, Peruzzotti-Jametti L, Pluchino S. The neural stem cell secretome and its role in brain repair. Brain Res. 2020;1729:146615.
36. Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med. 2010;5(1):121-43.
37. Mousavi M, Hedayatpour A, Mortezaee K, Mohamadi Y, Abolhassani F, Hassanzadeh G. Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination. Metab Brain Dis. 2019;34(4):1117-30.
38. Mahdavipour M, Hassanzadeh G, Seifali E, Mortezaee K, Aligholi H, Shekari F, et al. Effects of neural stem cell-derived extracellular vesicles on neuronal protection and functional recovery in the rat model of middle cerebral artery occlusion. Cell Biochem Funct. 2019.
39. Ijaz S, Mohammed I, Gholaminejhad M, Mokhtari T, Akbari M, Hassanzadeh G. Modulating Pro-inflammatory Cytokines, Tissue Damage Magnitude, and Motor Deficit in Spinal Cord Injury with Subventricular Zone-Derived Extracellular Vesicles. J Mol Neurosci. 2020;70(3):458-66.
40. Zhang H, Wang Y, Lv Q, Gao J, Hu L, He Z. MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage. Front Neurol. 2018;9:931-.
41. Slota JA, Booth SA. MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications. Noncoding RNA. 2019;5(2).
42. Roitbak T. MicroRNAs and Regeneration in Animal Models of CNS Disorders. Neurochem Res. 2019.
43. Obora K, Onodera Y, Takehara T, Frampton J, Hasei J, Ozaki T, et al. Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression. Scientific reports. 2017;7:43604.
44. Xu W, Gao L, Zheng J, Li T, Shao A, Reis C, et al. The Roles of MicroRNAs in Stroke: Possible Therapeutic Targets. Cell Transplant. 2018;27(12):1778-88.
45. Jeyaseelan K, Lim KY, Armugam A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008;39(3):959-66.
2. Bagheri A, Talei S, Hassanzadeh N, Mokhtari T, Akbari M, Malek F, et al. The neuroprotective effects of flaxseed oil supplementation on functional motor recovery in a model of ischemic brain stroke: upregulation of BDNF and GDNF. Acta Medica Iranica. 2017:785-92.
3. Cheng Y, Zhang J, Deng L, Johnson NR, Yu X, Zhang N, et al. Intravenously delivered neural stem cells migrate into ischemic brain, differentiate and improve functional recovery after transient ischemic stroke in adult rats. Int J Clin Exp Pathol. 2015;8(3):2928-36.
4. Alizamir T, Akbari M, Mokhtari T, Hassanzadeh G. Associated functional motor recovery induced by Intracerebroventricular (ICV) microinjection of Wharton’s jelly mesenchymal stem cells following brain ischemia/reperfusion injury in rat: Decreased dark neurons and Bax gene expression in the cerebral corte. Journal of Contemporary Medical Sciences. 2017;3(12).
5. Mehrannia K, Mokhtari T, Mogehi SMHN, Akbari M, Bazzaz JT, Mahakizeh S, et al. Intracerebroventricular injection of Wharton’s jelly mesenchymal stem cells attenuates brain damage in rat model of hypoxia: optimization of vascular endothelial growth factor and downregulation of inflammatory factors. Journal of Contemporary Medical Sciences. 2018;4(3).
6. Hao L, Zou Z, Tian H, Zhang Y, Zhou H, Liu L. Stem cell-based therapies for ischemic stroke. Biomed Res Int. 2014;2014:468748.
7. Takagi Y, Nishimura M, Morizane A, Takahashi J, Nozaki K, Hayashi J, et al. Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain. Journal of neurosurgery. 2005;103(2):304-10.
8. Baker EW, Kinder HA, West FD. Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function. Brain Behav. 2019;9(3):e01214.
9. Daadi MM, Maag AL, Steinberg GK. Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experimental stroke model. PLoS One. 2008;3(2):e1644.
10. Chang DJ, Oh SH, Lee N, Choi C, Jeon I, Kim HS, et al. Contralaterally transplanted human embryonic stem cell-derived neural precursor cells (ENStem-A) migrate and improve brain functions in stroke-damaged rats. Exp Mol Med. 2013;45:e53.
11. Yang ZB, Li TB, Zhang Z, Ren KD, Zheng ZF, Peng J, et al. The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke. Intern Med. 2016;55(10):1279-86.
12. Li M, Zhang J. Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Cardiovascular and Cerebrovascular Diseases. Biomed Res Int. 2015;2015:730535.
13. Bhalala OG, Srikanth M, Kessler JA. The emerging roles of microRNAs in CNS injuries. Nat Rev Neurol. 2013;9(6):328-39.
14. Wang C, Ji B, Cheng B, Chen J, Bai B. Neuroprotection of microRNA in neurological disorders (Review). Biomed Rep. 2014;2(5):611-9.
15. Wang Y, Wang Y, Yang GY. MicroRNAs in Cerebral Ischemia. Stroke Res Treat. 2013;2013:276540.
16. Martinez B, Peplow PV. Blood microRNAs as potential diagnostic and prognostic markers in cerebral ischemic injury. Neural Regen Res. 2016;11(9):1375-8.
17. Qiu J, Zhou XY, Zhou XG, Cheng R, Liu HY, Li Y. Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy. Biomed Res Int. 2013;2013:350419.
18. Huang X, Le QT, Giaccia AJ. MiR-210--micromanager of the hypoxia pathway. Trends Mol Med. 2010;16(5):230-7.
19. Meng ZY, Kang HL, Duan W, Zheng J, Li QN, Zhou ZJ. MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway. J Am Heart Assoc. 2018;7(5).
20. Chan YC, Banerjee J, Choi SY, Sen CK. miR-210: the master hypoxamir. Microcirculation. 2012;19(3):215-23.
21. Kim HW, Haider HK, Jiang S, Ashraf M. Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem. 2009;284(48):33161-8.
22. Zeng L, He X, Wang Y, Tang Y, Zheng C, Cai H, et al. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain. Gene Ther. 2014;21(1):37-43.
23. Zendedel A, Habib P, Dang J, Lammerding L, Hoffmann S, Beyer C, et al. Omega-3 polyunsaturated fatty acids ameliorate neuroinflammation and mitigate ischemic stroke damage through interactions with astrocytes and microglia. J Neuroimmunol. 2015;278:200-11.
24. Mokhtari T, Akbari M, Malek F, Kashani IR, Rastegar T, Noorbakhsh F, et al. Improvement of memory and learning by intracerebroventricular microinjection of T3 in rat model of ischemic brain stroke mediated by upregulation of BDNF and GDNF in CA1 hippocampal region. Daru. 2017;25(1):4.
25. Nemati S, Hatami M, Kiani S, Hemmesi K, Gourabi H, Masoudi N, et al. Long-term self-renewable feeder-free human induced pluripotent stem cell-derived neural progenitors. Stem Cells Dev. 2011;20(3):503-14.
26. Chen J, Hu R, Liao H, Zhang Y, Lei R, Zhang Z, et al. A non-ionotropic activity of NMDA receptors contributes to glycine-induced neuroprotection in cerebral ischemia-reperfusion injury. Sci Rep. 2017;7(1):3575.
27. Atlasi MA, Naderian H, Noureddini M, Fakharian E, Azami A. Morphology of Rat Hippocampal CA1 neurons following modified two and four-vessels global ischemia models. Archives of trauma research. 2013;2(3):124.
28. Takahashi K, Yasuhara T, Shingo T, Muraoka K, Kameda M, Takeuchi A, et al. Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells. Brain Res. 2008;1234:172-82.
29. Daadi MM, Hu S, Klausner J, Li Z, Sofilos M, Sun G, et al. Imaging neural stem cell graft-induced structural repair in stroke. Cell Transplant. 2013;22(5):881-92.
30. Beyer F, Samper Agrelo I, Kury P. Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models. Int J Mol Sci. 2019;20(2).
31. Ouyang Q, Li F, Xie Y, Han J, Zhang Z, Feng Z, et al. Meta-Analysis of the Safety and Efficacy of Stem Cell Therapies for Ischemic Stroke in Preclinical and Clinical Studies. Stem Cells Dev. 2019;28(8):497-514.
32. Barzegar M, Kaur G, Gavins FNE, Wang Y, Boyer CJ, Alexander JS. Potential therapeutic roles of stem cells in ischemia-reperfusion injury. Stem Cell Res. 2019;37:101421.
33. Bliss T, Guzman R, Daadi M, Steinberg GK. Cell transplantation therapy for stroke. Stroke. 2007;38(2 Suppl):817-26.
34. Liao LY, Lau BW, Sanchez-Vidana DI, Gao Q. Exogenous neural stem cell transplantation for cerebral ischemia. Neural Regen Res. 2019;14(7):1129-37.
35. Willis CM, Nicaise AM, Peruzzotti-Jametti L, Pluchino S. The neural stem cell secretome and its role in brain repair. Brain Res. 2020;1729:146615.
36. Baraniak PR, McDevitt TC. Stem cell paracrine actions and tissue regeneration. Regen Med. 2010;5(1):121-43.
37. Mousavi M, Hedayatpour A, Mortezaee K, Mohamadi Y, Abolhassani F, Hassanzadeh G. Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination. Metab Brain Dis. 2019;34(4):1117-30.
38. Mahdavipour M, Hassanzadeh G, Seifali E, Mortezaee K, Aligholi H, Shekari F, et al. Effects of neural stem cell-derived extracellular vesicles on neuronal protection and functional recovery in the rat model of middle cerebral artery occlusion. Cell Biochem Funct. 2019.
39. Ijaz S, Mohammed I, Gholaminejhad M, Mokhtari T, Akbari M, Hassanzadeh G. Modulating Pro-inflammatory Cytokines, Tissue Damage Magnitude, and Motor Deficit in Spinal Cord Injury with Subventricular Zone-Derived Extracellular Vesicles. J Mol Neurosci. 2020;70(3):458-66.
40. Zhang H, Wang Y, Lv Q, Gao J, Hu L, He Z. MicroRNA-21 Overexpression Promotes the Neuroprotective Efficacy of Mesenchymal Stem Cells for Treatment of Intracerebral Hemorrhage. Front Neurol. 2018;9:931-.
41. Slota JA, Booth SA. MicroRNAs in Neuroinflammation: Implications in Disease Pathogenesis, Biomarker Discovery and Therapeutic Applications. Noncoding RNA. 2019;5(2).
42. Roitbak T. MicroRNAs and Regeneration in Animal Models of CNS Disorders. Neurochem Res. 2019.
43. Obora K, Onodera Y, Takehara T, Frampton J, Hasei J, Ozaki T, et al. Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression. Scientific reports. 2017;7:43604.
44. Xu W, Gao L, Zheng J, Li T, Shao A, Reis C, et al. The Roles of MicroRNAs in Stroke: Possible Therapeutic Targets. Cell Transplant. 2018;27(12):1778-88.
45. Jeyaseelan K, Lim KY, Armugam A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 2008;39(3):959-66.
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Published
2020-06-26
How to Cite
Arab, L., Fanni, A., Nemati, S., Arefian, E., Ai, J., Mokhtari, T., … Hassanzadeh, G. (2020). Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210. Journal of Contemporary Medical Sciences, 6(3), 103–108. https://doi.org/10.22317/jcms.v6i3.781
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