At the interface of the immune system and the nervous system: how neuroinflammation modulates the fate of neural progenitors in vivo.
Neural stem and progenitor cells express a variety of receptors that enable them to sense and react to signals emanating from physiological and pathophysiological conditions in the brain as well as elsewhere in the body. Many of these receptors and were first described in investigations of the immune system, particularly with respect to hematopoietic stem cells. This emerging view of neurobiology has two major implications. First, many phenomena known from the hematopoietic system may actually be generalizable to stem cells from many organ systems, reflecting the cells' progenitor-mediated regenerative potential. Second, regenerative interfaces may exist between diverse organ systems; populations of cells of neuroectodermal and hematopoietic origin may interact to play a crucial role in normal brain physiology, pathology, and repair. An understanding of the origins of signals and the neural progenitors' responses might lead to the development of effective therapeutic strategies to counterbalance acute and chronic neurodegenerative processes. Such strategies may include modifying and modulating cells with regenerative potential in subtle ways. For example, stem cells might be able to detect pathology-associated signals and be used as "interpreters" to mediate drug and other therapeutic interventions. This review has focused on the role of inflammation in brain repair. We propose that resident astroglia and blood-born cells both contribute to an inflammatory signature that is unique to each kind of neuronal degeneration or injury. These cells play a key role in coordinating the neural progenitor cell response to brain injury by exerting direct and indirect environmentally mediated influence on neural progenitor cells. We suggest that investigations of the neural progenitor-immunologic interface will provide valuable data related to the mechanisms by which endogenous and exogenous neural progenitor cells react to brain pathology, ultimately aiding in the design of more effective therapeutic applications of stem cell biology. Such improvements will include: (1) ascertaining the proper timing for implanting exogenous neural progenitor cells in relation to the administration of anti-inflammatory agents; (2) identifying what types of molecules might be administered during injury to enhance the mobilization and differentiation of endogenous and exogenous neural progenitor cells while also inhibiting the detrimental aspects of the inflammatory reaction; (3) divining clues as to which molecules may be required to change the lesioned environment in order to invite the homing of reparative neural progenitor cells.
Mueller
F J
FJ
Program in Developmental Regenerative Cell Biology, The Burnham Institute, La Jolla, CA 92037, USA. franz-josef.mueller@gmx.de
McKercher
S R
SR
Imitola
J
J
Loring
J F
JF
Yip
S
S
Khoury
S J
SJ
Snyder
E Y
EY
D000818:Animals; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008954:Models, Biological; D009420:Nervous System / Q000473:pathology*; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000166:cytology