The neural stem cell secretome and its role in brain repair

Compelling evidence from experimental animal disease models and early-phase clinical trials identifies the transplantation of neural progenitor/stem cells (NSCs) as a viable path towards the development of clinically applicable exogenous stem cell therapies. Building from current advances in the field of NSC biology and following the positive outcomes of NSC transplantation studies, the contemporary view is that transplanted NSCs act as local 'factories' capable of producing and secreting a wide array of immune and neurotrophic factors. This has launched a 'stem cell race' to identify the mechanisms behind stem-cell mediated repair in what has been labeled the paracrine hypothesis. This hypothesis proposes that NSC grafts act as a natural source of potent biologics capable of modulating and promoting the restoration of several key functions in the central nervous system (CNS) tissue following acute or chronic tissue damage. Investigators have been inspired to examine novel ways to harness and utilize the pro-regenerative properties of NSC therapies as an alternative approach to a more classical (small molecule based) treatment of CNS diseases. In this review, we will discuss the most recent findings of human NSC (hNSCs) transplants in experimental animal models of CNS diseases that identify of hNSC-secreted factors, including those trafficked within extracellular membrane vesicles (EVs), and the outcomes of recent clinical trials utilizing hNSC therapeutics in CNS diseases.