Science to Practice: Genetic Engineering Meets Cell Tracking-A Promising Approach for Cell-based Therapies?

Cell-based therapies are gaining increasing importance and have been evaluated in many settings, including cancer, Parkinson disease, myocardial repair, stroke, and diabetes. In this context, it is of major importance that the cells are implanted into an optimal tissue environment and, correspondingly, that they reach the diseased region. Intravenous cell injection often is the route of choice, particularly if the cells are expected to circulate in the blood for longer periods of time and are able to actively migrate to the diseased tissue. Unfortunately, often only a small percentage of intravenously injected cells reach the target area. Higher accumulation can be achieved if the cells are injected into an artery that feeds the diseased area. However, in this case, fast blood velocities and substantial sheer stress make it difficult for the cells to adhere. In the study by Gorelik and colleagues (1), genetic engineering was used to overcome this limitation. Glial precursor cells were transiently transfected with very late antigen-4 (VLA-4) binding to vascular cell adhesion molecule-1 (VCAM-1), which is upregulated in inflamed endothelial cells. After labeling these cells with superparamagnetic iron oxide (SPIO) containing rhodamine, significantly increased binding to inflamed brain endothelial cells was shown and their homogeneous distribution over the inflamed brain tissue was convincingly demonstrated with magnetic resonance (MR) imaging and histologic examination. The authors concluded that transient transfection of SPIO-labeled cells with VLA-4 in combination with their arterial injection and the use of MR imaging monitoring may be an elegant way to increase the efficacy of cell-based treatments of inflammatory brain diseases.