Cell therapy for cerebral ischemia using vascular endothelial growth factor-secreting cells

To evaluate a potential neuroprotective role for vascular endothelial growth factor (VEGF) during ischemia, we grafted encapsulated VEGF-secreting cells into the brain parenchyma of a rat model of stroke. A genetically modified VEGF-secreting cell line (50–100 ng/10⁶cells/day) was established, and when encapsulated, these cells produced VEGF in a continuous and stable fashion for at least 2 months (30–50 ng/capsule/day). Recombinant human VEGF was delivered into the rat striatum at approximately the same delivery rate as that observed by the encapsulated cells (35 or 70 ng/day) for 6 days using a mini-osmotic pump. Six days after infusion, host animals received transient middle cerebral artery occlusion by the intraluminal suture technique. We found that the infarct volume in the VEGF infusion group was reduced by approximately 40% compared with vehicle infusion group. Furthermore, VEGF infusion caused significantly increased cerebral angiogenesis in the ischemic brain. In the penumbra area, the number of apoptotic cells in the VEGF infusion group was decreased significantly compared with that in vehicle group. These data show that the administration of a low-dose of VEGF into the parenchyma has both angiogenic and neuroprotective effects in the ischemic brain. Encapsulation and the grafting of genetically modified VEGF-secreting cells may be considered as a potentially effective therapy for the treatment of stroke in the future.