Engineered Cells Drive Blood Vessel Formation Following Stroke to Restore Lost Function in Mice

Researchers have recently demonstrated a cell therapy approach that drives greater blood vessel formation in the brain. In mice this treatment restores most of the loss of motor function that occurs following a stroke, a surprisingly large restoration given that the brain is notoriously lacking in regenerative capacity. Therapies capable of inducing greater blood vessel growth are of interest more generally in aging, as the density of capillary networks diminishes with age, contributing to cell and tissue dysfunction due to a reduced supply of nutrients and oxygen. An approach that allows for the safe restoration of capillary density throughout the body, and also the creation of greater redundancy in the network of larger vessels, could prove to be a useful preventative measure, reducing the impact of vascular aging.

Researchers have developed technology that can "retrain" skin cells to help repair damaged brain tissue. The nonviral tissue nanotransfection (TNT) technique effectively reprograms the skin cells to become vascular cells, which generate new blood vessels to help get blood to the damaged tissue. In tests, stroke-affected mice that received intracranial injections of the cells recovered nearly all of their motor function, and exhibited repair to damaged brain areas.

The newly reported approach uses TNT to introduce a key set of genes into skin cells, which then drive direct reprogramming of the cells into vascular cells. For their mouse studies, the team pre-conditioned the cells by introducing a cocktail containing the developmental transcription factor genes Etv2, Foxc2, and Fli1 (collectively, EFF) and injected the cells back into the stroke-affected brains, where they triggered the formation of new blood vessels to deliver blood supply to the tissue and help to repair damage.

The team's experiments found that mice given this cell therapy regained 90% of their motor function, with MRI scans showing that damaged areas of the brain were repaired within a few weeks. "MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Our results indicate that intracranial delivery of fibroblasts nanotransfected with the EFF cocktail leads to dose-dependent increases in perfusion, reduced stroke volume, and significant recovery of locomotive abilities in stroke-affected mice. We found that the mice have a higher recovery because the cells that are being injected into the affected area also release healing signals in the form of vesicles that help in the recovery of damaged brain tissue."

Link: https://www.genengnews.com/news/cell-therapy-aids-stroke-damaged-brain-repair-restores-90-of-motor-function/

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