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

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 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 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 attenuates 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.

Intrahippocampal transplantation of dental pulp stem cells improved memory function and reduced neuroinflammation-induced cell death in the rat’s model of seizure

“…NFTs have a key role in the creation of an appropriate neural microenvironment via the promotion of neural differentiation, neuronal survival, axon regeneration, and neurite outgrowth (Luzuriaga et al 2021). Recently, many cell-based strategies have been conducted to assess the pre-clinical e cacy of different types of MSCs for the treatment of epilepsy including; bone marrow-derived mesenchymal stem cells (BMSCs) (Salem et al 2018), Adipose tissue-derived mesenchymal stem cells (ADSCs) (Wang et al 2021), human umbilical mesenchymal stem cell (HU-MSC) (Mohammed et al 2014, Huang et al 2016, and dental pulp stem cells (DPSCs) (Senthilkumar et al 2022). MSCs have also attracted attention in the clinical eld as a potential therapeutic option for the treatment of epilepsy which can reduce the frequency of seizures (Hlebokazov, Dakukina et al 2017, Milczarek et al 2018).…”