Feasibility and Efficacy of Intra-Arterial Administration of Embryonic Stem Cell Derived-Mesenchymal Stem Cells in Animal Model of Alzheimer's Disease

摘要

Mesenchymal stem cells (MSCs) promote functional recoveries in pathological experimental models of the central nervous system and are currently being tested in clinical trials for neurological disorders. However, no studies have examined the various roles of embryonic stem cell derived (ES)-MSCs in eliciting therapeutic effects for Alzheimer's disease (AD). In the present study, we investigated the neuroprotective effect of ES-MSCs in cellular and animal models of AD, as well as the safety of the intra-arterial administration of ES-MSCs in an AD animal model. ES-MSCs displayed higher cell viability than that of bone marrow (BM)-MSCs in amyloid-beta (A beta)-induced cellular models. Moreover, the efficacy of autophagy induction in ES-MSCs was comparable to that of BM-MSCs; however, intracellular A beta levels were more significantly reduced in ES-MSCs than in BM-MSCs. In a rat model of AD, ES-MSCs significantly inhibited A beta-induced cell death in the hippocampus and promoted autophagolysosomal clearance of A beta, which was concomitantly followed by decreased levels of A beta in the hippocampus. Furthermore, ES-MSC treatment in A beta-treated rats featured a higher memory performance than that of rats injected solely with A beta. Finally, intra-arterial administration of an appropriate cell density of ES-MSCs was safe and free from in situ occlusion or cerebral ischemia. These data support the therapeutic potential of ES-MSCs and clinical applications of the intra-arterial route of ES-MSC administration in AD.