Reversal of Neuropsychiatric Comorbidities in an Animal Model of Temporal Lobe Epilepsy Following Systemic Administration of Dental Pulp Stem Cells and Bone Marrow Mesenchymal Stem Cells.

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2023-01-01 DOI:10.2174/1566523223666221027113723

Sivapriya Senthilkumar, Krishnamoorthi Maiya, Nishta Kusum Jain, Mata Sundeep, Snehal Mangaonkar, Prajnya Prabhu, Kiranmai S Rai, Bindu M Kutty, Anandh Dhanushkodi

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Abstract

Introduction: We aim to investigate whether timed systemic administration of dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BM-MSCs) with status epilepticus (SE) induced blood-brain barrier (BBB) damage could facilitate the CNS homing of DPSCs/BM-MSCs and mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of Temporal Lobe epilepsy (TLE).

Background: Cognitive impairments, altered emotional responsiveness, depression, and anxiety are the common neuropsychiatric co-morbidities observed in TLE patients. Mesenchymal stem cells (MSCs) transplantation has gained immense attention in treating TLE, as ~30% of patients do not respond to anti-epileptic drugs. While MSCs are known to cross the BBB, better CNS homing and therapeutic effects could be achieved when the systemic administration of MSC is timed with BBB damage following SE.

Objectives: The objectives of the present study are to investigate the effects of systemic administration of DPSCs/BM-MSCs timed with BBB damage on CNS homing of DPSCs/BM-MSCs, neurodegeneration, neuroinflammation and neuropsychiatric comorbidities in an animal model of TLE.

Methodology: We first assessed the BBB leakage following kainic acid-induced SE and timed the intravenous administration of DPSCs/BM-MSCs to understand the CNS homing/engraftment potential of DPSCs/BM-MSCs and their potential to mitigate neurodegeneration, neuroinflammation and neuropsychiatric comorbidities.

Results: Our results revealed that systemic administration of DPSCs/BM-MSCs attenuated neurodegeneration, neuroinflammation, and ameliorated neuropsychiatric comorbidities. Three months following intravenous administration of DPSCs/BM-MSCs, we observed a negligible number of engrafted cells in the corpus callosum, sub-granular zone, and sub-ventricular zone.

Conclusion: Thus, it is evident that functional recovery is still achievable despite poor engraftment of MSCs into CNS following systemic administration.

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颞叶癫痫动物模型全身应用牙髓干细胞和骨髓间充质干细胞后神经精神合并症的逆转

在颞叶癫痫(TLE)动物模型中，我们的目的是研究在癫痫持续状态(SE)诱导的血脑屏障(BBB)损伤中，定时全身给药牙髓干细胞(DPSCs)或骨髓间充质干细胞(BM-MSCs)是否能促进DPSCs/BM-MSCs的中枢神经系统归家，减轻神经退行性变、神经炎症和神经精神合并症。背景:认知障碍、情绪反应改变、抑郁和焦虑是TLE患者常见的神经精神合并症。间充质干细胞(MSCs)移植在治疗TLE中获得了极大的关注，因为约30%的患者对抗癫痫药物没有反应。虽然已知间充质干细胞可以穿过血脑屏障，但如果在SE后血脑屏障损伤的同时给药，则可以获得更好的中枢神经系统归巢和治疗效果。目的:本研究的目的是研究在脑屏障损伤的动物模型中，全身给药DPSCs/BM-MSCs对中枢神经系统归巢、神经退行性变、神经炎症和神经精神合并症的影响。方法:我们首先评估了kainic酸诱导SE后的血脑屏障渗漏，并定时静脉给药DPSCs/BM-MSCs，以了解DPSCs/BM-MSCs的中枢神经系统归家/植入潜力，以及它们减轻神经退行性疾病、神经炎症和神经精神合并症的潜力。结果:我们的研究结果显示，全身给药DPSCs/BM-MSCs可减轻神经退行性变、神经炎症和改善神经精神合并症。静脉注射DPSCs/BM-MSCs 3个月后，我们观察到胼胝体、亚颗粒区和脑室下区植入的细胞数量可以忽略不计。结论:因此，尽管MSCs在全身给药后植入中枢神经系统的能力较差，但功能恢复仍然是可以实现的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.