The present study used in vitro and in vivo
stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from
oxygen glucose deprivation. Adult rats that were subjected to
middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in
infarct area and peri-
infarct cell loss, much better than
intravenous administration. The optimal dose was 7.5 × 106 cells/mL when delivered via the intracarotid artery within 3 days poststroke, although
therapeutic effects persisted even when administered at 1 week after
stroke. Compared with other mesenchymal stem cells, NCS-01 cells ameliorated both the structural and functional deficits after
stroke through a broad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as
basic fibroblast growth factor and
interleukin-6, but equally importantly we observed for the first time the formation of filopodia by NCS-01 cells under
stroke conditions, characterized by
cadherin-positive processes extending from the stem cells toward the ischemic cells. Collectively, the present efficacy readouts and the novel filopodia-mediated mechanism of action provide solid lab-to-clinic evidence supporting the use of NCS-01 cells for treatment of
stroke in the clinical setting.