TY - JOUR
T1 - 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
AU - Senthilkumar, Sivapriya
AU - Maiya, Krishnamoorthi
AU - Jain, Nishta Kusum
AU - Mata, Sundeep
AU - Mangaonkar, Snehal
AU - Prabhu, Prajnya
AU - Rai, Kiranmai S.
AU - Kutty, Bindu M.
AU - Dhanushkodi, Anandh
N1 - Funding Information:
This study is supported by the Department of Biotechnology, Government of India to AD (BT/PR10915/ MED/31/260/2014) and Indian Council of Medical Research, Government of India to AD (No.55/5/2014-NIMHANS-3/BMS) and Intramural funding from Manipal Academy of Higher Education, Manipal.
Funding Information:
This study is supported by the Department of Biotechnology, Government of India to AD (BT/PR10915/ MED/31/260/2014) and Indian Council of Medical Re-search, Government of India to AD (No.55/5/2014-NIMHANS-3/BMS) and Intramural funding from Manipal Academy of Higher Education, Manipal.
Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85161951396
UR - https://www.scopus.com/inward/citedby.url?scp=85161951396&partnerID=8YFLogxK
U2 - 10.2174/1566523223666221027113723
DO - 10.2174/1566523223666221027113723
M3 - Article
C2 - 36305152
AN - SCOPUS:85161951396
SN - 1566-5232
VL - 23
SP - 198
EP - 214
JO - Current Gene Therapy
JF - Current Gene Therapy
IS - 3
ER -