Article

Cellular repair of CNS disorders: An immunological perspective

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Human Molecular Genetics (Impact Factor: 6.39). 04/2008; 17(R1):R84-92. DOI: 10.1093/hmg/ddn104
Source: PubMed

ABSTRACT

Cellular repair is a promising strategy for treating central nervous system (CNS) disorders. Several strategies have been
contemplated including replacement of neurons or glia that have been lost due to injury or disease, use of cellular grafts
to modify or augment the functions of remaining neurons and/or use of cellular grafts to protect neural tissue by local delivery
of growth or trophic factors. Depending on the specific disease target, there may be one or many cell types that could be
considered for therapy. In each case, an additional variable must be considered—the role of the immune system in both the
injury process itself and in the response to incoming cells. Cellular transplants can be roughly categorized into autografts,
allografts and xenografts. Despite the immunological privilege of the CNS, allografts and xenografts can elicit activation
of the innate and adaptive immune system. In this article, we evaluate the various effects that immune cells and signals may
have on the survival, proliferation, differentiation and migration/integration of transplanted cells in therapeutic approaches
to CNS injury and disease.

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    • "This response of hESC DA neurons to guidance cues provides an additional criterion to monitor the differentiation of hESC DA neurons in vitro and to determine if they are mimicking their native counterparts in vivo, and may thus act as appropriate replacements for diseased DA neurons in PD patients. hESC DA neurons can still respond to guidance cues in the presence of cytokines Inflammatory cytokines have pleiotropic effects in the central nervous system, but their potential effects on neuron health or function after transplantation therapy is not well understood (Chen and Palmer, 2008). Inflammatory cytokines can inhibit spinal cord regeneration (Nakamura et al., 2003), and TNFα is implicated in the progression of PD (Sriram et al., 2002). "
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    • "We could also show in the present study that L1 overexpressing SENAs, in comparison to the wild-type SENAs, decreased the number of microglial cells in the host tissue. The reason why the number of microglial cells was decreased in the vicinity of L1 overexpressing versus wild-type grafts is currently not understood but encourages further investigation of the role of L1 on immune system cells in the brain as the immune response of the brain to injury and grafted tissue is an important issue in neurodegenerative diseases and in stem cell biology (Barker and Widner, 2004; Chen and Palmer, 2008; Ideguchi et al., 2008). "
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