Topically applied adipose-derived mesenchymal stem cell treatment in experimental focal cerebral ischemia

In this study, the neuro-modulation effect of topical mesenchymal stem cells (MSCs) was tested in a rodent middle carotid artery occlusion (MCAO) model. Twenty-four hours after MCAO, craniotomy was made and 0.8 × 10⁶ GFP-MSCs were topically applied to the exposed parietal cortex. The MSCs were fixed in position by a thin layer of fibrin glue (N = 30). In the control group, saline were topically applied to the ipsilateral parietal cortex (N = 30). Three days after topical application, few GFP-positive cells were found in the ischemic penumbra. They expressed GFAP and NeuN. Topical MSCs triggered microglial activation, astrocytosis and cellular proliferation at day 3. The recovery of neurological functions were significantly enhanced as determined in Rotarod test and Morris Water Maze test with smaller infarct volume. PCR array showed that expressions of ten genes of neurogenesis were altered in the penumbra region (fold change > 1.25, p < 0.05) in MSCs group: Apoe, Ascl1, Efnb1, Mef2c, Nog, A100a6 and B2m were up-regulated; Pax2, Pax3 and Th were down-regulated. In conclusion, topical application provided a direct and effective transplant method for the delivery of MSCs to the surface of ipsilateral cerebral cortex and the topical MSCs could improve the neurological function from cerebral ischemia resulting from a major cerebral artery occlusion in a rodent experimental model.