Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral andhistological readouts and mechanistic insights into stem celltherapy

No clue what this said or how you are going to train your doctor on this.

Translating intracarotid artery transplantation of bone marrow-derived NCS-01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy

Yuji Kaneko1| Jea-Young Lee1| Naoki Tajiri1| Julian P. Tuazon1|Trenton Lippert1| Eleonora Russo1| Seong-Jin Yu1| Brooke Bonsack1|Sydney Corey1| Alexandreya B. Coats1| Chase Kingsbury1| Thomas N. Chase2|Minako Koga2| Cesar V. Borlongan11Center of Excellence for Aging and BrainRepair, Department of Neurosurgery and BrainRepair, University of South Florida College ofMedicine, Tampa, Florida2KM Pharmaceutical Consulting LLC,Washington, District of ColumbiaCorrespondenceCesar V. Borlongan, Department ofNeurosurgery and Brain Repair, University ofSouth Florida Morsani College of Medicine,12901 Bruce B Downs Blvd, Tampa, FL,33612.Email: cborlong@usf.edu 

Abstract 

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-01cells. 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 reductionsin infarct area and periinfarct cell loss, much better than intravenous administration.The optimal dose was 7.5×106cells/mL when delivered via the intracarotid artery within 3 days post stroke, although therapeutic effects persisted even when administered at 1 week after stroke. Compared with other mesenchymal stem cells, NCS-01cells ameliorated both the structural and functional deficits after stroke through abroad therapeutic window. NCS-01 cells secreted therapeutic molecules, such as basic fibroblast growth factor and interleukin-6, but equally importantly we observedfor 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