Neural stem cell niches and homing: recruitment and integration into functional tissues.

Garzón-Muvdi T, Quiñones-Hinojosa A.

The Johns Hopkins Hospital, Department of Neurosurgery, Brain Stem Cell Laboratory, Johns Hopkins University, Baltimore, MD 21231, USA.

Considerable attention has focused on the study of neural stem cells (NSCs) as therapy for neurodegenerative diseases. The mammalian brain harbors NSCs throughout life mainly in the subventricular zone (SVZ) as well as the subgranular zone. NSCs in the SVZ are a specialized subpopulation of astrocytes that maintain contact with the ventricle and vascular structures. Components of the SVZ microenvironment, or niche, include intercellular interactions, extracellular matrix proteins, and soluble factors, all of which aid in NSC proliferation, self-renewal, and multipotentiality. Multiple studies demonstrate that endogenous neurogenesis responds to insults such as ischemic stroke, multiple sclerosis and other neurodegenerative diseases, and even brain tumors, supporting the existence of remarkable plasticity and significant regenerative potential in the mammalian brain. Further, in response to recruitment cues from damaged brain tissue NSCs not only "home" to sites of disease but also integrate into functional tissues and appear to acquire the morphological and physiological properties of neurons, astrocytes, and oligodendrocytes. In this review we focus on neurogenesis in the SVZ and on recruitment cues that promote homing and integration of NSCs to sites of disease in the brain. We also discuss animal models of important human neurodegenerative diseases in which transplantation of neural stem cells has been tested.