Piotr Walczak1,2, Michael Levy2,3, Michael Gorelik2,3, Douglas A. Kerr2,3, Jeff W.M Bulte1,2
1Radiology, Johns Hopkins University, Baltimore, MD, USA; 2Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA; 3Neurology, Johns Hopkins University, Baltimore, MD, USA
Global cerebral targeting and homing of therapeutic stem cells is of key importance for neurodegenerative disorders having multiple lesions. For cell therapy using intra-arterial injections, it is critical to achieve a high level of initial cellular adhesion to cerebral endothelium before cells can enter the brain parenchyma. We have exploited the use of the VLA-4/VCAM-1 endothelial adhesion pathway to enhance initial endothelial binding by means of transfecting glial restricted precursors (GRPs) with VLA-4. In an LPS-induced inflammatory brain model, Feridex-labeled and VLA-4 over-expressing GRPs showed a dramatically enhanced global cerebral retention as compared to those injected in normal brain.