Title: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
Volume: 23
Issue: 3
Author(s): Sivapriya Senthilkumar, Krishnamoorthi Maiya, Nishta Kusum Jain, Sundeep Mata, Snehal Mangaonkar, Prajnya Prabhu, Kiranmai S. Rai, Bindu M. Kutty and Anandh Dhanushkodi*
Affiliation:
- Manipal Institute of Regenerative Medicine, Bangalore, Manipal Academy of Higher Education, Manipal, India
Keywords:
DPSC, migration, cognition, neuroprotection, hippocampus, TLE.
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.