Therapeutic window for treatment of cortical ischemia with bone marrow-derived cells in rats.

The beneficial effect of treatment with bone marrow mononuclear cells (BMMCs) was evaluated in different therapeutic windows in a rat model of focal ischemia induced by thermocoagulation of the blood vessels in the left motor, somestesic, and sensorimotor cortices. We also compared the therapeutic benefits between BMMCs and bone marrow-derived mesenchymal stem cells (MSCs). BMMCs and MSCs were obtained from donor rats and injected into the jugular vein after ischemia. BMMCs-treated animals received approximately 3x10(7) cells at post-ischemic days (PIDs) 1, 7, 14, or 30. MSCs-treated animals received approximately 3x10(6) cells at PIDs 1 and 30. Control animals received only the vehicle. The animals were then evaluated for functional sensorimotor recovery weekly with behavioral tests (cylinder test and adhesive test). Significant recovery of sensorimotor function was only observed in the cylinder test in animals treated with BMMCs at PIDs 1 and 7. Similar effects were also observed in the animals treated with MSCs 1 day after ischemia, but not in animals treated with MSCs 30 days after ischemia. Significant decrease in glial scarring did not seem to be a mechanism of action of BMMCs, since treatment with BMMCs did not change the level of expression of GFAP, indicating no significant change in the astrocytic scar in the periphery of the ischemic lesion. These results suggest that BMMCs might be an efficient treatment protocol for stroke only in the acute/subacute phase of the disease, and its efficiency in inducing functional recovery is similar to that of MSCs.