P-EP013. Superior migration propensity of dental pulp stem cells in in vitro and in vivo models of excitotoxic neurodegeneration

Abstract

Introduction. Mesenchymal stem cell therapy has gained colossal attention as a therapeutic alternative in treating neurodegenerative diseases (ND). The challenges in cell-based therapy comprises of defining a suitable cell type expressing homing factors, the precise injection/administration timing based on blood brain barrier (BBB) dynamics and the route of administration that would aid in functional recovery. Even though, bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in treating spectrum of diseases, the limitations like painful bone marrow extraction, modest yield and poor CNS engraftment following systemic injections prompt to search for an alternate source of MSCs. We hypothesize that neural crest derived dental pulp stem cells (DPSC) would be a better candidate for treating ND due to its ease isolation, higher yield and for their inherent propensity towards neural lineage. We investigated the migratory potential of DPSC vs BM-MSC in in- vitro and in vivo models of kainic acid (KA) induced neurodegeneration. Methods. Trans-well, matrigel, and chorioallantoic membrane (CAM) migration assays were carried out in an in vitro model of neurodegeneration. We assessed the CNS engraftment potential of DPSC/BM-MSC following intravenous administration in animal model of KA mediated hippocampal neurodegeneration and also studied the role of BBB damage after excitotoxicity to facilitate efficient homing of DPSC/BM-MSC. Functional recovery was assessed by a battery of behavioural tests after stem cell injection. Results. Following KA treatment to neurons in vitro, the migration potential of DPSC towards the degenerating site was significantly higher than BM-MSC. To validate the in vitro observations, KA administration resulted in BBB damage and intravenous administration of DPSC in synchronization with KA mediated BBB damage resulted in prominent CNS engraftment and behavioral recovery compared to BM-MSC. Conclusion. Neural crest originated DPSC might possess better CNS engraftment following systemic injection.