Manipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, India.
Department of Physiology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Curr Gene Ther. 2023;23(3):198-214. doi: 10.2174/1566523223666221027113723.
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).
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.
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.
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.
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.
Thus, it is evident that functional recovery is still achievable despite poor engraftment of MSCs into CNS following systemic administration.
我们旨在研究在诱导血脑屏障（BBB）损伤的情况下，有癫痫发作（SE）病史的牙髓干细胞（DPSCs）或骨髓间充质干细胞（BM-MSCs）的定时全身给药是否能促进 DPSCs/BM-MSCs 的中枢神经系统归巢，并减轻颞叶癫痫（TLE）动物模型中的神经退行性变、神经炎症和神经精神共病。
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共病。间充质干细胞（MSCs）移植在治疗 TLE 方面引起了广泛关注，因为约 30%的患者对抗癫痫药物没有反应。虽然已知 MSCs 可以穿过 BBB，但当 SE 后 BBB 损伤时进行 MSC 的系统给药，可以更好地实现 CNS 归巢和治疗效果。
本研究的目的是研究在 TLE 动物模型中，与 BBB 损伤同步进行的 DPSCs/BM-MSCs 的全身给药对 DPSCs/BM-MSCs 的中枢神经系统归巢、神经退行性变、神经炎症和神经精神共病的影响。
我们首先评估了海人酸诱导的 SE 后的 BBB 渗漏，并定时给予 DPSCs/BM-MSCs 的静脉内给药，以了解 DPSCs/BM-MSCs 的中枢神经系统归巢/植入潜力及其减轻神经退行性变、神经炎症和神经精神共病的潜力。
我们的结果表明，DPSCs/BM-MSCs 的全身给药减轻了神经退行性变、神经炎症，并改善了神经精神共病。静脉内给予 DPSCs/BM-MSCs 三个月后，我们在胼胝体、颗粒下区和侧脑室下区观察到很少有植入的细胞。
因此，尽管在系统给药后 MSCs 向中枢神经系统的植入效果不佳，但仍能实现功能恢复，这一点是显而易见的。
