Immuno-Therapeutic Potential of Haematopoietic and Mesenchymal Stem Cell Transplantation in MS
Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College Building 560/Burlington Danes, Room E415, Imperial College London, 160 Du Cane Road, London, UK. Results and problems in cell differentiation
02/2009; 51:237-57. DOI: 10.1007/400_2008_14
In the last few years there has been extraordinary progress in the field of stem cell research. Two types of stem cells populate the bone marrow: haematopoietic stem/progenitor cells (HSC) and mesenchymal stem cells (MSC). The capacity of HSC to repopulate the blood has been known and exploited therapeutically for at least four decades. Today, haematopoietic stem cell transplantation (HSCT) holds a firm place in the therapy of some haematological malignancies, and a potential role of HSCT for treatment of severe autoimmune diseases has been explored in small-scale clinical studies. Multiple sclerosis (MS) is the noncancerous immune mediated disease for which the greatest number of transplants has been performed to date. The results of clinical studies are double-faced: on the one hand, HSCT has demonstrated powerful effects on acute inflammation, arresting the development of focal CNS lesions and clinical relapses; on the other hand, the treatment did not arrest chronic worsening of disability in most patients with secondary progressive MS, suggesting limited or no beneficial effects on the chronic processes causing progressive disability. MSC are a more recent addition to the range of experimental therapies being developed to treat MS. While interest in MSC usage was originally raised by their potential capacity to differentiate into different cell lineages, recent work showing their interesting immunological properties has led to a revised concept, envisioning their utilization for immuno-modulatory purposes. In this review we will summarize the current clinical and experimental evidence on HSC and MSC and outline some key questions warranting further investigation in this exciting research area.
Available from: PubMed Central
- "HSCs are also able to home to the damaged sites (Kavanagh and Kalia, 2011). HSC transplantation has gained much consideration as therapy for hematological malignancies and for the treatment of severe autoimmune diseases (Muraro and Uccelli, 2010). "
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ABSTRACT: Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neuro-developmental disorders with core symptoms of dysfunctions in social interactions and communication skills, restricted interests, repetitive - stereotypic verbal and non-verbal behaviors. Biomolecular evidence points to complex gene-environmental interactions in ASDs. Several biochemical processes are associated with ASDs: oxidative stress (including endoplasmic reticulum stress), decreased methylation capacity, limited production of glutathione; mitochondrial dysfunction, intestinal dysbiosis, increased toxic metal burden, and various immune abnormalities. The known immunological disorders include: T-lymphocyte populations and function, gene expression changes in monocytes, several autoimmune-related findings, high levels of N-acetylgalactosaminidase (which precludes macrophage activation), and primary immune deficiencies. These immunological observations may result in minicolumn structural changes in the brain, as well as, abnormal immune mediation of synaptic functions. Equally, these immune dysregulations serve as the rationale for immune-directed interventions such as hematopoietic stem cells (HSCs), which are pivotal in controlling chronic inflammation and in the restoration of immunological balance. These properties make them intriguing potential agents for ASD treatments. This prospective review will focus on the current state-of-the-art knowledge and challenges intrinsic in the application of HSCs for ASD-related immunological disorders.
Frontiers in Immunology 06/2013; 4:140. DOI:10.3389/fimmu.2013.00140
Available from: Bruno Gran
- "Mast cell Luteolin No (Theoharides, 2009) Enhancing endogenous immune regulatory mechanisms Up-regulation of Treg cells Retinoic acid Yes (small study plus IFN) (Massacesi et al., 1991; Vergelli et al., 1997; Qu et al., 1998) (Sewell et al., 2002; Sewell et al., 2003; Correale and Farez, 2009) Gut parasites Phase I trials ongoing; Larger trials pending Enhancement of endogenous type 1 IFN TLR ligands Yes (polyI:C) (Bever et al., 1991) (Touil et al., 2006; O'Brien et al., 2010) Cell-based therapies Transfer of Treg Transfer of CD4+CD25+ Treg cells No (Stephens et al., 2009) Haematopoietic stem cell treatment Immunosuppression and immune system renewal Yes (Karussis et al., 1992; 1993; 1999; Burt et al., 1998; van Bekkum, 2000; Burt et al., 2009; Muraro and Uccelli, 2010; Pasquini et al., 2010 "
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ABSTRACT: Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions.
British Journal of Pharmacology 03/2011; 164(4):1079-106. DOI:10.1111/j.1476-5381.2011.01302.x · 4.84 Impact Factor
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ABSTRACT: Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations/ variants thereof.
In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required.
Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role.
The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level.
Surgical Neurology International 12/2010; 1(1):93. DOI:10.4103/2152-7806.74240 · 1.18 Impact Factor
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