Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia

Intravenous transplantation of mesenchymal stem cells (MSCs) prepared from bone marrow ameliorates functional deficits in rat cerebral infarction models. Although several hypotheses to account for these therapeutic effects have been suggested, angiogenesis is thought to be largely responsible. MSCs were intravenously infused into rats in the relatively later time points after permanent middle cerebral artery occlusion (MCAO) to determine if they could contribute to neovascularization and functional recovery. Although MRI analysis revealed that only rats receiving MSCs 7days after MCAO exhibited decreased ischemic lesion volume than the control group, all MSCs treated rats receiving MSCs up to 1month after MCAO had greater angiogenesis near the border of the ischemic lesions and showed greater functional recovery in the treadmill stress test than did control rats. Thus, these results suggest that the time window of MSC therapy is at least over 1 month after cerebral infarction in the rat permanent MCAO model, and systemic delivery of MSCs in the later phase after cerebral ischemia may have beneficial effect through an angiogenic mechanism.