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Cross-talk between neural stem cells and immune cells: the key to better brain repair?

Abstract

Systemic or intracerebral delivery of neural stem and progenitor cells (NSPCs) and activation of endogenous NSPCs hold much promise as potential treatments for diseases in the human CNS. Recent studies have shed new light on the interaction between the NSPCs and cells belonging to the innate and adaptive arms of the immune system. According to these studies, the immune cells can be both beneficial and detrimental for cell genesis from grafted and endogenous NSPCs in the CNS, and the NSPCs exert their beneficial effects not only by cell replacement but also by immunomodulation and trophic support. The cross-talk between immune cells and NSPCs and their progeny seems to determine both the efficacy of endogenous regenerative responses and the mechanism of action as well as the fate and functional integration of grafted NSPCs. Better understanding of the dialog between NSPCs and innate and adaptive immune cells is crucial for further development of effective strategies for CNS repair.

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Figure 1: Cells of the innate (microglia, monocytes, monocyte-derived macrophages) and adaptive (T and B cells) immune arms have either detrimental or beneficial effects on neurogenesis both in vitro and in vivo.
Figure 2: After transplantation, NSPCs derived from different sources (embryonic stem cells, fetal and adult brain, reprogrammed somatic cells) promote CNS repair using several mechanisms collectively named stem cell therapeutic plasticity.
Figure 3: The extent of tissue regeneration in vivo driven by grafted multipotent NSPCs depends on the efficacy of the different activities such cells adopt after transplantation.

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All authors are supported by European Union FP7 collaborative grant TargetBraIn (no. 279017).

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Kokaia, Z., Martino, G., Schwartz, M. et al. Cross-talk between neural stem cells and immune cells: the key to better brain repair?. Nat Neurosci 15, 1078–1087 (2012). https://doi.org/10.1038/nn.3163

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