240PED

Rezumat

  Cerebral ischemia is a devastating of the brain without regenerative treatment options, demanding a vigorous search for new therapeutic strategies. Despite the initial hope that cell-based therapies may stimulate restorative processes in the ischemic brain, it is now recognized that aging processes may promote generate an unfavorable environment for such treatments. By this project we take advantage of our previous experience on stroke therapies and recent advances in tissue engineering have developed injectable hydrogels that can provide both a mechanical support and trophic factors for neuronal precursor cells (NPCs). In this project, we propose to develop a new technology to promote regeneration in the damaged brain area by applying three layers of hydrogels in sequence, thereby recreating a neurovascular niche by recruitment of neural precursor cells and microvascular cells. Specifically, the first layer is formed by a hydrogel connecting the periinfarct with the stroke cavity (“biobridge”) containing a mixture of microvascular endothelial cells/pericytes; this will be followed by a hydrogel layer containing primed neuronal stem cells that are generated either by explants of the subventricular zone primed for increased neurogenesis by applying small currents to animals’ ears or isolated neuronal stem cells from the primed subventricular zone embedded in a nourishing hydrogel; finally the stroke cavity will be sealed by a protective hydrogel layer containing microvascular endothelial cells and dermal fibroblasts. Successful creation of the neurovascular niche will be investigated using immunohistological methods as well as behavioral tests. Through this novel experimental technique we expect a significant improvement in tissue integrity and functional restoration after stroke. Given the overwhelming importance of stroke therapy for both patients and society, this approach, if successful, will be a breakthrough in the field.