Background and purpose: Cell transplantation therapy hold great potential to improve impairments after cerebral ischemia. However, it is still unclear whether donor age affects structural and functional recovery after cell therapy. Here, we investigate the hypothesis that donor age (Young vs. Old) drastically affects the repair mechanism after cell transplantation for ischemic stroke.
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 derived from 24 years old man (Young) and MSC derived from 64 years old man (Old) via internal carotid artery. Behavioral recovery was assessed with modified Neurological severity score (mNSS) until 21 days (D21) after stroke. Animals were euthanized at D21, and histological analysis was performed regarding neovascularization and neurogenesis.
Results: Young showed a significant recovery in mNSS (3.7±0.6) compared with Control (6.1±0.5) or Old (5.2±0.7) at D21 (P<0.01). Immunohistological analysis revealed that the number of RECA-1 and PDGFR-1β double positive vessels much increased in Young (113±48.6/mm2) compared with that in Control (61.5±35.9/mm2) or Old (76.9±36.9/mm2) suggesting vessel maturation (P <0.01). Interestingly, direction of the astrocyte process, defined as direction index, significantly correlated with the number of Msi-1 positive neural stem cells (P<0.01, r=0.27; Spearman), and direction index with many neural stem cells was significantly higher in Young compared with Old (P <0.05).
Conclusions: Donor age drastically affects the host environment and functional recovery after cell transplantation for ischemic stroke. This study revealed that direction of the astrocyte contributed to neural stem cell migration into the periinfarct area. Young hMSC was superior to old hMSC in structural and functional recovery after ischemic stroke.