Intracarotid Injection of Fluorescence Activated Cell-Sorted CD49d-Positive Neural Stem Cells Improves Targeted Cell Delivery and Behavior After Stroke in a Mouse Stroke Model

Abstract

Background and Purpose-Intravascular delivery of neural stem cells (NSCs) after stroke has been limited by the low efficiency of transendothelial migration. Vascular cell adhesion molecule-1 is an endothelial adhesion molecule known to be upregulated early after stroke and is responsible for the firm adhesion of inflammatory cells expressing the surface integrin, CD49d. We hypothesize that enriching for NSCs that express CD49d and injecting them into the carotid artery would improve targeted cell delivery to the injured brain. Methods-Mouse NSCs were analyzed for the expression of CD49d by fluorescence activated cell sorting. A CD49d-enriched (CD49d ϩ ) (Ͼ95%) and -depleted (CD49d -; Ͻ5%) NSC population was obtained by cell sorting. C57/Bl6 mice underwent left-sided hypoxia-ischemia surgery and were assigned to receive 3ϫ10 5 CD49d ϩ , CD49d

Endovascular Methods for Stem Cell Transplantation

“…Therefore, based on the findings in this thesis, considerations should be made that CD29CD49dVCAM-1 interaction is one of the best studied crosstalk mechanisms on how immunological cells leave the bloodstream to perform homing to disease ridden tissue where inflammation occurs (Elices et al 1990). This line of reasoning is supported by other studies implicating VCAM-1 interaction in both ischemic stroke and muscle dystrophy pre-clinical studies (Gavina et al 2006;Guzman et al 2008). An interesting comparison can be made regarding diapedesis in cell systems aimed for transplantation compared to immunological cells.…”

“…VCAM-1 is also implicated both as a model of treatment for immunological modulation of the inflammatory responses following CNS insults and as surface antigen for cell treatment of CNS insults. In one study, fluorescence activated cell sorting (FACS) was performed for the expression of CD49d and identifying it as one of the important factors for directing diapedesis (Guzman et al 2008). This finding has received a lot of interest from different fields, among other it has been shown that VCAM-1 expression has a critical role in transplantation of cells in dystrophic muscle (Gavina et al 2006).…”

“…hMSCs showed a broad expression of integrins, commonly expressed by immune cells, that are important for diapedesis through the vessel endothelium and subsequent migration into the parenchyma. Specifically, analysis of the heterodimers forming receptors for ICAM-1 and VCAM-1 were analyzed, based on previous work indicating CD49d expression as important for successful intra-vasal transplantations (Guzman et al 2008). Thus, probably the most interesting finding was the CD49d signal of 68 in hMSC as opposed to 0.4 in hNPC (p=0.0047).…”

Intravascular cell replacement therapy for stroke

“…Reports have indicated that after stereotactic intraparenchymal, 17,46 intracerebroventricular, 60 intravenous, 12,13,89 and intraarterial transplantation, 32,53,73,74 stem cells can home to sites of injury in the CNS and induce functional recovery. Of these various transplantation techniques, those that depend on intravascular delivery of stem cells for stroke are particularly attractive.…”

BDNF Pretreatment of Human Embryonic-Derived Neural Stem Cells Improves Cell Survival and Functional Recovery after Transplantation in Hypoxic–Ischemic Stroke

“…In the field of intravascular neural stem cell (NSC) transplantation, our lab has shown a direct correlation between the number of cells surviving in the brain after intra-arterial (IA) transplantation and positive functional outcomes (13). However, intravascular transplantation of human NSCs into rodents has often demonstrated a very low rate of cell engraftment (5).…”