Targeting Ischemic Stroke with Neural Stem Cells: Insights into Endogenous Repair Mechanisms, Biomaterial-Based Delivery, and Exosome Therapies.

Neurological diseases, such as stroke, are typically deemed refractory because of the adult mammalian brain's poor ability to self-repair and regenerate, resulting in irreparable cellular damage. Neural stem cells (NSCs) have distinct capabilities to regenerate themselves and differentiate into several types of neural lineage cells, including neurons and glial cells, making them valuable in the treatment of stroke. They are capable of differentiating into neurons and glial cells, which establish themselves within the integrated circuitry of neural networks and restore functions. NSCs can also facilitate beneficial alterations indirectly, by secreting neurotrophic factors and exosomes that promote neuronal survival, angiogenesis, and dampen inflammation. NSCs promote an endogenous adaptive immune response toward a neuroprotective state, which enhances repair processes and reduces the impact of ischemic inflammation. Nevertheless, significant obstacles faced by directly transplanted NSCs are their limited survival and unpredictable differentiation in vivo. In order to address the constraints of directly transplanted NSCs and considering the pathological characteristics of stroke including the loss of a certain cell type, extensive research has focused on investigating the possibility of enhancing the in vivo survival, migration, and differentiation of NSCs. In light of this, different strategies, such as preconditioning of NSCs, using NSC exosome, and also cell delivery by biomaterials, have gained significant interest. In this study, we delve into current advancements in harnessing NSC capacities to enhance neurogenesis and induce neuroprotection in stroke.