http://www.sciencedirect.com/science/article/pii/S0163725813001691
- Dep. of Morphology & Biomedical Research Institute, Hasselt University, Belgium
Abstract
The
pharmacological support and stimulation of endogenous and transplanted
neural stem cells (NSCs) is a major challenge in brain repair. Trauma to
the central nervous system (CNS) results in a distinct inflammatory
response caused by local and infiltrating immune cells. This makes
NSC-supported regeneration difficult due to the presence of inhibitory
immune factors which are upregulated around the lesion site. The
continual and dual role of the neuroinflammatory response leaves it
difficult to decipher upon a single modulatory strategy. Therefore,
understanding the influence of cytokines upon regulation of NSC
self-renewal, proliferation and differentiation is crucial when
designing therapies for CNS repair. There is a plethora of partially
conflicting data in vitro and in vivo on the role of
cytokines in modulating the stem cell niche and the milieu around NSC
transplants. This is mainly due to the pleiotropic role of many factors.
In order for cell-based therapy to thrive, treatment must be
phase-specific to the injury and also be personalized for each patient,
i.e. taking age, sex, neuroimmune and endocrine status as well as other
key parameters into consideration. In this review, we will summarize the
most relevant information concerning interleukin (IL)-1, IL-4, IL-10,
IL-15, IFN-γ, the neuropoietic cytokine family and TNF-α in order to
extract promising therapeutic approaches for further research. We will
focus on the consequences of neuroinflammation on endogenous brain stem
cells and the transplantation environment, the effects of the above
cytokines on NSCs, as well as immunopharmacological manipulation of the
microenvironment for potential therapeutic use.
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