Multiple Sclerosis and Stem Cell Therapy
What is MS?
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.
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.
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]
Mesenchymal Stem Cell-Based Therapy in a Mouse Model of Experimental Autoimmune Encephalomyelitis (EAE).
Mesenchymal Stem Cell-Based Therapy in a Mouse Model of Experimental Autoimmune Encephalomyelitis (EAE). Methods Mol Biol. 2014;1213:303-319 Authors: Bowles AC, Scruggs BA, Bunnell BA Abstract Multiple sclerosis (MS) is a common neurodegenerative disease that presents after an auto-reactive immune response against constituents of the central nervous system. Demyelination, inflammation, and white matter lesions are all hallmarks of this disease. Clinical research supports the use of mesenchymal stem cells (MSCs) as therapy for MS to ameliorate symptoms and pathology. MSCs can be isolated from multiple tissues, including adipose and bone marrow, and are able to migrate to sites of pathology, release anti-inflammatory factors, and provide immunomodulatory and neuroprotective effects once administered. Numerous studies have demonstrated the beneficial effects of MSCs in experimental autoimmune encephalomyelitis (EAE), an induced model of MS. EAE can be induced in several species; however, the mouse is commonly used for therapeutic testing. In the following chapter, scientists will be able to learn how to prepare reagents and MSCs (e.g., isolate, culture, and expand) as well as skillfully execute induction of EAE in mice and administer stem cell-based treatments. Standard methods used to evaluate the disease progression and analyze postmortem tissues are also included. PMID: 25173393 [PubMed - as supplied by publisher]Read more...