Systemically administered human bone marrow-derived mesenchymal stem home into peripheral organs but do not induce neuroprotective effects in the MCAo-mouse model for cerebral ischemia

Abstract

Mesenchymal stem cells (MSC) from bone marrow induce neuroprotective effects and improve clinical symptoms in animal models for acute cerebral ischemia. So far only few data are available from the murine system. Moreover, no data exist regarding neuroprotective effects depending on the application route. Because most preclinical trials regarding restorative therapy in stroke are performed in mice, we aimed to investigate the neuroprotective capacities of human MSC (hMSC) in the middle cerebral artery occlusion (MCAo)-mouse model of cerebral ischemia. As systemic transplantation of MSC could provide a gentle therapeutic procedure for the (mostly elderly) stroke patients, we analyzed effects of this application at a clinically relevant time point. Bone marrow-derived hMSCs were administered intravenously 24h after MCAo. Mortality and clinical outcome of the transplanted mice did not differ from PBS-treated controls. After 3 and 7 days hMSC were robustly detected in lung, spleen, kidney and intestine, but not in the brain. MRI measurements revealed no differences in infarct size in hMSC injected animals compared to controls. In the neurogenic subventricular zone and the dentate gyrus no significant increase of endogenous cell proliferation was detected following systemic hMSC transplantation. This data further prove the week neurogenic and neuroprotective effect and the limitations of systemically administered hMSCs in cerebral ischemia.