Cellular repair of CNS disorders: An immunological perspective

ArticleinHuman Molecular Genetics 17(R1):R84-92 · April 2008with9 Reads
DOI: 10.1093/hmg/ddn104 · Source: PubMed
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.
    • "The greatest advantage in the use of autologous cells is definitely to avoid immunological responses host-versus-graft. Furthermore during therapy with autologous cells you can prevent the immunosuppressive treatment on the patient, avoiding the risk of infections and lowering by far the costs of the therapy (Chen and Palmer, 2008). In bioaesthetic treatment this approach seems to be most suitable for the less intrusive therapies and look more natural given by the patient's own cells (Tsai et al., 2000). "
    [Show abstract] [Hide abstract] ABSTRACT: Craniofacial area represent a unique district of human body characterized by a very high complexity of tissues, innervation and vascularization, and being deputed to many fundamental function such as eating, speech, expression of emotions, delivery of sensations such as taste, sight and earing. For this reasons, tissue loss in this area following trauma or for example oncologic resection, have a tremendous impact on patients’ quality of life. In the last 20 years regenerative medicine has emerged as one of the most promising approach to solve problem related to trauma, tissue loss, organ failure etc. One of the most powerful tools to be used for tissue regeneration is represented by stem cells, which have been successfully implanted in different tissue/organs with exciting results. Nevertheless both autologous and allogeneic stem cell transplantation raise many practical and ethical concerns that make this approach very difficult to apply in clinical practice. For this reason different cell free approaches have been developed aiming to the mobilization, recruitment and activation of endogenous stem cells into the injury site avoiding exogenous cells implant but instead stimulating patients’ own stem cells to repair the lesion. To this aim many strategies have been used including functionalized bioscaffold, controlled release of stem cell chemoattractants, growth factors, BMPs, Platelet–Rich-Plasma and other new strategies such as ultrasound wave and laser are just being proposed. Here we review all the current and new strategies used for activation and mobilization of endogenous stem cells in the regeneration of craniofacial tissue.
    Full-text · Article · Feb 2016
    • "Future work is needed to test if more clinically relevant cells, for example, iNSCs derived from human fibroblasts or blood cells converted with fewer factors in a non-integrative manner, would work in small and large PD animal models. The iNSCs used in this study had the same genetic background as the recipient PD mice, and should not elicit adaptive immune recognition in host (Chen et al., 2011; Chen and Palmer, 2008). The low survival rate of grafts may reflect a relatively vulnerable feature of this cell line, compared to iPSC-derived DA precursor cells (Wernig et al., 2008), which, however, have an inherent problem of tumorigenicity. "
    [Show abstract] [Hide abstract] ABSTRACT: Lmx1a plays a central role in the specification of dopaminergic (DA) neurons, which potentially could be employed as a key factor for trans-differentiation to DA neurons. In our previous study, we have converted somatic cells directly into neural stem cell-like cells, namely induced neural stem cells (iNSCs), which further can be differentiated into subtypes of neurons and glia in vitro. In the present study, we continued to test whether these iNSCs have therapeutic effects when transplanted into a mouse model of Parkinson's disease (PD), especially when Lmx1a was introduced into these iNSCs under a Nestin enhancer. iNSCs that over-expressed Lmx1a (iNSC-Lmx1a) gave rise to an increased yield of dopaminergic neurons and secreted a higher level of dopamine in vitro. When transplanted into mouse models of PD, both groups of mice showed decreased ipsilateral rotations; yet mice that received iNSC-Lmx1a vs. iNSC-GFP exhibited better recovery. Although few iNSCs survived 11weeks after transplantation, the improved motor performance in iNSC-Lmx1a group did correlate with a greater tyrosine hydroxylase (TH) signal abundance in the lesioned area of striatum, suggesting that iNSCs may have worked through a non-autonomous manner to enhance the functions of remaining endogenous dopaminergic neurons in brain. Copyright © 2014. Published by Elsevier B.V.
    Full-text · Article · Oct 2014
    • "shiverer mouse) (Ben-Hur et al., 2005; Duncan et al., 2011 ) or chemically induced demyelination (Blakemore and Franklin, 2008), intraparenchymal transplantation of many different myelinating cell types extensively remyelinates denuded axons (Windrem et al., 2004; Buchet et al., 2011; Sim et al., 2011). In contrast, cell replacement has been only partially satisfactory in a persistently unfavourable environment, where different cell sub-populations in different CNS areas are affected and where the tissue architecture is altered, such as in stroke, spinal cord injury (SCI), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) (Chen and Palmer, 2008). In stroke and SCI animal models, NPCs from multiple sources have been demonstrated to functionally integrate into the host neural circuits and differentiate into neurons (Kelly et al., 2004; Cummings et al., 2005; Buhnemann et al., 2006; Yan et al., 2007; Daadi et al., 2009; Braz et al., 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Regenerative processes occurring under physiological and pathological (reparative) conditions are a fundamental part of life, and they vary greatly among different species, individuals and tissues. Physiological regeneration occurs naturally as a consequence of normal cell turnover, or as an inevitable outcome of any biological process requiring the restoration of homeostasis. Reparative regeneration occurs as a consequence of tissue damage. Although the central nervous system (CNS) has been considered for years as a ‘perennial’ tissue, it is now becoming clear that both physiological and reparative regeneration occur within the CNS to sustain tissue homeostasis and repair. Neural progenitor cells (NPCs) residing within the healthy CNS are emerging as crucial actors in both physiological as well as pathological conditions. Thus, a large number of experimental stem cell–based transplantation systems for CNS repair have recently been established, suggesting that transplanted NPCs might promote tissue repair not only via cell replacement but also via bystander (paracrine) mechanisms favourably influencing the diseased tissue milieu.
    Full-text · Chapter · Apr 2014 · Stem Cell Research
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