Abstract
Various cell-based therapeutic strategies have been investigated for vascular and tissue regeneration after ischemic stroke. We have developed a novel cell population, called regeneration-associated cells (RACs), by quality- and quantity-controlled culture of unfractionated mononuclear cells. RACs were trans-arterially injected into 10-week-old syngeneic male mice at 1, 3, 5 or 7 days after permanent middle cerebral artery occlusion (MCAO) to determine the optimal timing for administration in terms of outcome at day 21. Next, we examined the effects of RACs injection at day 1 after MCAO on neurological deficits, infarct volume, and mediators of vascular regeneration and anti-inflammation at days 7 and 21. Infarct volume at day 21 was significantly reduced by transplantation of RACs at day 1 or 3. RACs injected at day 1 reduced the infarct volume at day 7 and 21. Angiogenesis and anti-inflammatory mediators, VEGF and IL-10, were increased at day 7, and VEGF was still upregulated at day 21. We also observed significantly enhanced ink perfusion in vivo, tube formation in vitro, and definitive endothelial progenitor cell colonies in colony assay. These results suggest that RAC transplantation in MCAO models promoted significant recovery of neural tissues through intensified anti-inflammatory and angiogenic effects.
Highlights
Recent treatments for acute ischemic stroke are mostly focused on vascular recanalization, including interventional treatments and intravenous thrombolysis, which have a narrow therapeutic time windows after onset
With the aim of obtaining endothelial progenitor cells (EPCs)-enriched cell populations for clinical application with simple and economical methodology, we have recently developed a novel cell population, named regeneration-associated cells (RACs), by means of quality- and quantitycontrolled culture of unfractionated mononuclear cells (MNCs) [14, 15] in the presence of human recombinant stem cell factor (SCF), thrombopoietin, Flt-3 ligand, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6)
There was no significant difference in Bederson score, body weight, body temperature or CBF among the PBS, MNCs, and RACs-treated groups at any cell administration timing after middle cerebral artery occlusion (MCAO)
Summary
Recent treatments for acute ischemic stroke are mostly focused on vascular recanalization, including interventional treatments and intravenous thrombolysis, which have a narrow therapeutic time windows after onset. These treatments have only benefited relatively small numbers of stroke patients. Edaravone is available as a brain-protective therapy in the acute phase of ischemic stroke, but has so far been approved only in Japan. Regeneration-associated cells cure ischemic stroke funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript Edaravone is available as a brain-protective therapy in the acute phase of ischemic stroke, but has so far been approved only in Japan. [1] On the other hand, pioneering approaches using embryonic stem cells [2] and induced pluripotent stem cells [3] have been devised, and there is increasing preclinical and clinical evidence that transplantation of specific somatic stem cells or progenitor cells, such as endothelial progenitor cells (EPCs), can promote recovery from ischemic cerebral injury. [4,5,6,7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
