Open AccessTranslating intracarotid artery transplantation of bone marrow‐derived NCS‐01 cells for ischemic stroke: Behavioral and histological readouts and mechanistic insights into stem cell therapy
Author(s) -
Kaneko Yuji,
Lee JeaYoung,
Tajiri Naoki,
Tuazon Julian P.,
Lippert Trenton,
Russo Eleonora,
Yu SeongJin,
Bonsack Brooke,
Corey Sydney,
Coats Alexandreya B.,
Kingsbury Chase,
Chase Thomas N.,
Koga Minako,
Borlongan Cesar V.
Publication year - 2020
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.19-0229
Subject(s) - medicine , mesenchymal stem cell , stroke (engine) , stem cell , cell therapy , transplantation , neural stem cell , bone marrow , in vivo , progenitor cell , stem cell therapy , filopodia , pathology , neuroscience , cell , biology , microbiology and biotechnology , mechanical engineering , genetics , engineering
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 × 10 6 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.