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Our goal is to develop a cellular strategy for repairing the damage seen in children's myelin disease, Multiple Sclerosis and other neurological diseases.
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Wednesday, February 27, 2002
British charities prepare to boost the UK's lead in stem cell research.Guardian Unlimited Politics | Special Reports | Millions in grants for embryo stem cell research "Millions of pounds of funding for research on stem cells from human embryos is expected to be announced in the next few months as at least four universities gear up to consolidate Britain's reputation as the world capital of stem cell and cloning research." Tuesday, February 19, 2002
ScienceDaily Magazine -- Neural Stem Cells Move To Damaged Areas Of Brain After Injury; Adult Mammalian Brain Has Potential To Heal Itself, Says Scientist Primitive neural cells in the brains of laboratory rats respond to acute brain injuries by moving to the injured area and attempting to form new neurons, according to University of Michigan neurologist Jack M. Parent, M.D. Understanding how this self-repair mechanism works could someday help physicians reduce brain damage caused by strokes or neurodegenerative diseases. Friday, February 15, 2002
With this letter, I wish to bring to your attention work that may be of some relevance to diseases of demyelination. Aspects of this work you can find on the website: http://www.nonpharmaceutical.com/ Specifically, several people with multiple sclerosis have shown considerable improvements with the consumption of alkaline magnesium bicarbonate solution. The principle behind this improvement is complex. It involves neutralisation of the inflammatory response in the brain by negating the acidity of lysosomes in inflammatory cells. CMRI NOTE: Unsubstantiated to date. Dr. Jacek Kwiecien of McMaster writes: Today I spoke to Dr. Ira Black, (MD), neurologist, Chair of the Department of Neuroscience and Cell Biology at the Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey. I had met Dr. Black at the Neural Stem Cell workshop in France in April. He coaxed, in a simple way, stromal cells from the rat and apparently, human bone marrow to become neurons with high (80%) efficiency. He published this work in the Journal of Neuroscience Research in 2000 and suggested I try (I already talked to Dr. Doering about it) to isolate stromal cells from bone marrow to start with. He asked me to call him back after the Neuroscience Meeting, in a week and a half so that we can discuss stromal marrow cells in adult shakers to see whether they would form myelin. He was successful in making neurons from these cells both in vitro and in vivo in normal rats but not oligodendrocytes. It is logical for me (and he agrees) to hypothesize that if non-neuronal cells can be made to become neurons, they may respond to the environment of the CNS of adult, or other dysmyelinated or demyelinated CNS and differentiate into oligodendrocytes. I do not have a proof of principle here, but this experiment can be quickly performed given the fact that cells are easy to obtain and we can transplant them into the LES rats when we are ready. I am quite excited about this possibility, provided it works because bone marrow is easily accessible, abundant tissue in the body, and the stromal cells are not only easy to expand in culture but also can be manipulated to become certain cell type before transplantation. We will see how it develops. As you probably know, there was a substantial noise about it in the media in August, a researcher from Montreal isolated/developed neural stem cells from a mouse skin. This work was published in Nature Medicine and the author is the invited speaker to the Neural regeneration meeting in California in December. I am anxious to talk to her about ways she made skin a source of neural stem cells and whether her cell lines thus obtained can become oligodendrocytes. CELLULAR PLASTICITY IN THE CNS OF ADULT DYSMYELINATED RATS.J.M. Kwiecien, K.H. Delaney, J. Wang, S. Jiang, M.P. Rathbone, D.L. Kirkham, L.C. Doering. Department of Pathology and Molecular Medicine and Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. The Long Evans Shaker (LES) and Bouncer Long Evans (LE-bo) rats lack myelin in the CNS but have lifespan similar to that of normal laboratory rat. The LES has a dysfunctional MBP gene with a large retrotransposonal insertion in the non-coding DNA sequence flanking the exon 3. The LE-bo phenotype may be related to identical mutation in the MBP gene but the LES and LE-bo phenotypes are distinct. In a study of kinetics of glial cell proliferation in the spinal cord, the maximum suppression of mitotic activity is delayed in the LES, at 8 weeks of age, and in the LE-bo, at 16 weeks, and is never complete. Then mitotic activity increases and peaks at 16-20 weeks in the LES and at 28 weeks in the LE-bo. Ultra-structurally, severe dysmyelination and progressive accumulation of a membranous material in the perikaryon of oligodendrocytes coincides with futile attempts at myelination. Immature oligodendroglia are prevalent in both adult mutants. Although myelination is arrested in the LES at 40-69 weeks, it is unabated in the LE-bo up to 45 weeks of age. Widespread axonal sprouting is evident in the CNS of adult LES and LE-bo. The right 13th thoracic dorsal nerve root (T13) of adult LES rats, was cut and re-sutured to its point of entry in the spinal cord. After 3 weeks, a crystal of DiI was placed on the end of a 2-3 mm stump of the right T13. Morphology of the DiI fluorescence at the level of T13 indicates abundant regeneration of central axons of right T13 DRG into the right dorsal horn. Neural cell cultures from the subependymal region of the lateral ventricle of adult rat brain were established and cells surviving in nutrition-depleted conditions formed floating neurospheres exposed to a combination of bFGF and EGF mitogens. 5 mL of a supension of neurospheres, was injected into the spinal cord at the T13 level of 16 week old LES. After 4 weeks, some of transplanted cells were associated with myelin sheets around adjacent axons. The LES and LE-bo rats are animal models suitable for studies on cellular and molecular mechanisms regulating regenerative processes in the adult CNS including axonal regeneration and remyelination. Supported by: The Canadian Myelin Research Initiative, The Multiple Sclerosis Society of Canada, The J.P. Bickell Foundation, The Department of Pathology and Molecular Medicine and Faculty of Health Sciences, McMaster University. |