Abstract W P89: Functional Recovery Depends on Donor Age after Stem Cell Transplantation for Stroke

Abstract

Introduction: Cell transplantation therapy hold great potential to improve impairments after cerebral ischemia. However, it is still unclear whether the donor age affects functional recovery after cerebral ischemia. Here, we investigate the hypothesis that donor age (young vs. old) drastically affects the repair mechanism after cell transplantation for stroke. Materials and methods: Male Sprague Dawley rats were subjected to transient middle cerebral artery occlusion. At 24 hours after stroke, rats were randomly assigned to receive PBS (control), human mesenchymal stem cells (MSC) derived from 24 years old man (young MSC) and MSC derived from 64 years old man (old MSC) via internal carotid artery. Behavioral recovery was assessed with modified Neurological severity score (mNSS) until 21 days after stroke. Animals were euthanized at 21 days, and histological analysis was performed regarding inflammatory reaction, neovascularization and endogenous stem cell activation. Result: Young MSC showed an significant recovery in mNSS (3.7±0.6) compared with control (6.1±0.5) and old MSC (5.2±0.7) at 21 days after stroke (P<0.01). In histological analysis, infarct volume was not significantly different among the groups. However, IBA-1 positive microglia was significantly inhibited in young MSC (9.3±5.9%) compared with control (22.1±13.1%) and old MSC (15.2%±14.2%) both in the peri-infarct cortex and striatum (P<0.01). Moreover, RECA-1 positive vessels significantly increased in young MSC (5.4±1.1%) compared with control (5.0±1.6%) and old MSC (4.6%±1.5%) in the peri-infarct cortex (P<0.01). Interestingly, Young MSC showed massive GFAP positive reactive astrocyte running radially into the peri-infarct area with Musashi-1 (Msi-1) positive neural progenitor cells. Conclusion: Donor age drastically affect the host environment, endogenous progenitor cell activation and functional recovery after cell transplantation for stroke.