Transfection of Noggin in bone marrow stromal cells (BMSCs) enhances BMSC‐induced functional outcome after stroke in rats

Abstract

Early intervention with intravenous administration of bone marrow stromal cells (BMSCs) reduces infarction size and ameliorates functional deficits in rat ischemia models. Noggin, an inhibitor of bone morphogenetic protein (BMP), has been demonstrated to provide protection from ischemic disease. In the present work, we hypothesize that administering Noggin-transfected BMSCs enhances BMSC-induced brain repair after cerebral ischemia. We compared the effects of BMSCs alone and Noggin-transfected BMSCs (Noggin-BMSCs) systematically delivered into the middle cerebral artery occlusion (MCAo) rat model. Noggin expression in BMSCs was achieved using adenoviral infection together with a green fluorescent protein (GFP) vector to monitor transduction efficiency and facilitate posttransplantation tracking. BMSCs and Noggin-BMSCs were intravenously injected into the rats 6 hr after MCAo. At 7 days after MCAo, the GFP-expressing BMSCs and Noggin-BMSCs were found primarily in the ischemic penumbra, which indicated that the intravenously delivered cells survived and reached in the lesion site. Both BMSC and Noggin-BMSC treatment significantly promoted neurogenesis in the ipsilateral subventrical zone (SVZ), reduced infarct volume, and led to functional improvement compared with the control group. Moreover, these beneficial effects were significantly greater in the Noggin-BMSC-treated group compared with BMSCs alone treatment (P < 0.05). Noggin expression in the ischemic hemisphere was significantly increased in the Noggin-BMSC-treated group as revealed by enzyme-linked immunosorbent assay (ELISA) at 7 days after MCAo compared with BMSC-treated and control groups (P < 0.05). These results indicate that transfection of Noggin in BMSCs enhances BMSC-induced neuroprotective effects when administered intravenously during the acute phase after stroke.