Multiple Sclerosis Stem Cell Treatment

Multiple Sclerosis and Stem Cell Therapy

What is MS?

Multiple Sclerosis and Stem Cell Treatment

Multiple Sclerosis and Stem Cell Therapy

Multiple sclerosis is also known as disseminated sclerosis or encephalomyelitis disseminata.

It is an inflammatory disease where the fatty myelin sheaths around the axons of the brain and spinal cord are damaged. The disease often leads to demyelination and scarring.

The disease usually appears in young adults and is more common in women. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other.

Nerve cells communicate by sending electrical signals called action potentials down long fibers called axons, which are wrapped in an insulating substance called myelin.

In MS, the body's own immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals.

The name multiple sclerosis refers to scars (scleroses—better known as plaques or lesions) particularly in the white matter of the brain and spinal cord, which is mainly composed of myelin.

Although much is known about the mechanisms involved in the disease process, the cause remains unknown. There is currently no known cure for multiple sclerosis and treatments attempt to return function after an attack, prevent new attacks, and prevent disability.

 

Multiple Sclerosis and Stem Cell Therapy

Immune Reconstitution after Double Umbilical Cord Blood Stem Cell Transplantation: Comparison with Unrelated Peripheral Blood Stem Cell Transplantation.


2011 Aug 26. [Epub ahead of print]

Jacobson CA, Turki AT, McDonough SM, Stevenson KE, Kim HT, Kao G, Herrera MI, Reynolds CG, Alyea EP, Ho VT, Koreth J, Armand P, Chen YB, Ballen K, Soiffer RJ, Antin JH, Cutler CS, Ritz J.


Source Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, Massachusetts.


Abstract
Double umbilical cord blood (DUCB) transplantation is an accepted transplantation strategy for patients without suitable human leukocyte antigen (HLA) matched donors. However, DUCB transplantation is associated with increased morbidity and mortality because of slow recovery of immunity and a high risk of infection. To define the differences in immune reconstitution between DUCB transplantation and HLA matched unrelated donor (MUD) transplantation, we performed a detailed, prospective analysis of immune reconstitution in 42 DUCB recipients and 102 filgrastim-mobilized unrelated peripheral blood stem cell recipients.

Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort compared with the MUD cohort for 1 to 6 months posttransplantation (P < .001), including naive (CD45RO-) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25) T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the DUCB cohort and numbers remained significantly greater from 3 to 24 months after transplantation (P = .001).

CD56CD16 natural killer (NK) cells also recovered more rapidly in DUCB recipients and remained significantly greater from 1 to 24 months after transplantation. B cell activating factor (BAFF) levels were higher in the DUCB cohort at 1 month (P < .001), were similar in both cohorts at 3 and 6 months, and were lower in the DUCB cohort at 12 months (P = .002). BAFF/CD19 B cell ratios were lower in the DUCB cohort at 3 (P = .045), 6 (P = .02), and 12 months (P = .002) after transplantation. DUCB recipients had more infections within the first 100 days after transplantation (P < .001), and there was less chronic graft-versus-host disease (P < .001), but there were no differences in cumulative incidence of relapse, nonrelapse death, progression-free survival, or overall survival between the 2 groups. These results suggest that increased risk of infections is specifically associated with delayed reconstitution of all major T cell subsets, but the increased risk is limited to the first 3 months after DUCB transplantation. There is no increased risk of relapse, suggesting that graft-versus-leukemia activity is maintained. Early reconstitution of B cells and NK cells may, in part, account for these findings.


PMID: 21875503 [PubMed - as supplied by publisher]

 

Adult stem cells and multiple sclerosis.

Cell Prolif. 2011 Apr;44 Suppl 1:35-8

Authors: Scolding N

Multiple sclerosis (MS) is a common neurological disease and a major cause of disability, particularly affecting young adults.

It is characterized by patches of damage occurring throughout the brain and spinal cord, with loss of myelin sheaths - the insulating material around nerve fibres that allows normal conduction of nerve impulses - accompanied by loss of cells that make myelin (oligodendrocytes).

 

In addition, we now know that there is damage to nerve cells (neurones) and their fibres (axons) too, and that this occurs both within these discrete patches and in tissue between them. The cause of MS remains unknown, but an autoimmune reaction against oligodendrocytes and myelin is generally assumed to play a major role, and early acute MS lesions almost invariably show prominent inflammation.

Efforts to develop cell therapy in MS have long been directed towards directly implanting cells capable of replacing lost oligodendrocytes and regenerating myelin sheaths.

Accordingly, the advent of techniques to generate large numbers of oligodendrocytes from embryonic stem cells appeared a significant step towards new stem cell treatments for MS; while the emerging consensus that adult stem cells from, for example, the bone marrow had far less potential to turn into oligodendrocytes was thought to cast doubt on their potential value in this disease.

A number of scientific and medical concerns, not least the risk of tumour formation associated with embryonic stem cells, have however, prevented any possible clinical testing of these cells in patients.

 

More recently, increasing understanding of the complexity of tissue damage in MS has emphasized that successful cell therapy may need to achieve far more than simply offering a source of replacement myelin-forming cells.

The many and varied reparative properties of bone marrow-derived (mesenchymal) stem cells may well offer new and attractive possibilities for developing cell-based treatments for this difficult and disabling condition.

PMID: 21481041 [PubMed - in process]

Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes Infect. 2014 Sep 10; Authors: Jasmin, Jelicks LA, Tanowitz HB, Peters VM, Mendez-Otero R, Campos de Carvalho AC, Spray DC Abstract Chagasic cardiomyopathy, resulting from infection with the parasite Trypanosoma cruzi, was discovered more than a century ago and remains an incurable disease. Due to the unique properties of mesenchymal stem cells (MSC) we hypothesized that these cells could have therapeutic potential for chagasic cardiomyopathy. Recently, our group pioneered use of nanoparticle-labeled MSC to correlate migration with its effect in an acute Chagas disease model. We expanded our investigation into a chronic model and performed more comprehensive assays. Infected mice were treated with nanoparticle labeled MSC and their migration was correlated with alterations in heart morphology, metalloproteinase activity, and expression of several proteins. The vast majority of labeled MSC migrated to liver, lungs and spleen whereas a small number of cells migrated to chagasic hearts. Magnetic resonance imaging (MRI) demonstrated that MSC therapy reduced heart dilatation. Additionally metalloproteinase activity was higher in heart and other organs of infected mice. Protein expression analyses revealed that connexin 43, laminin γ1, IL-10 and INF-γ were affected by the disease and recovered after cell therapy. Interestingly, MSC therapy led to upregulation of SDF-1 and c-kit in the hearts. The beneficial effect of MSC therapy in Chagas disease is likely due to an indirect action of the cells of the heart, rather than the incorporation of large numbers of stem cells into working myocardium. PMID: 25218054 [PubMed - as supplied by publisher]
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Systems-Based Technologies in Profiling the Stem Cell Molecular Framework for Cardioregenerative Medicine. Stem Cell Rev. 2014 Sep 14; Authors: Wyles SP, Faustino RS, Li X, Terzic A, Nelson TJ Abstract Over the last decade, advancements in stem cell biology have yielded a variety of sources for stem cell-based cardiovascular investigation. Stem cell behavior, whether to maintain its stable state of pluripotency or to prime toward the cardiovascular lineage is governed by a set of coordinated interactions between epigenetic, transcriptional, and translational mechanisms. The science of incorporating genes (genomics), RNA (transcriptomics), proteins (proteomics), and metabolites (metabolomics) data in a specific biological sample is known as systems biology. Integrating systems biology in progression with stem cell biologics can contribute to our knowledge of mechanisms that underlie pluripotency maintenance and guarantee fidelity of cardiac lineage specification. This review provides a brief summarization of OMICS-based strategies including transcriptomics, proteomics, and metabolomics used to understand stem cell fate and to outline molecular processes involved in heart development. Additionally, current efforts in cardioregeneration based on the "one-size-fits-all" principle limit the potential of individualized therapy in regenerative medicine. Here, we summarize recent studies that introduced systems biology into cardiovascular clinical outcomes analysis, allowing for predictive assessment for disease recurrence and patient-specific therapeutic response. PMID: 25218144 [PubMed - as supplied by publisher]
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