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Role of Stem Cells in Future Therapy of Multiple Sclerosis
#1
Multiple sclerosis (MS) is chronic demyelinating, inflammatory autoimmune disease of the central nervous system. This disease gives permanent lesion to the central nervous system. This autoimmune disease attacks parts of myelin sheath. This myelin sheath has role in insulation of neural communication. Destruction of oligodendrocytes is damaging the communication between two cells, because oligodendrocytes receive impulses via axon of another neural cell. Primary etiology of MS remains unknown and it is possible that it has more than one cause. This disease affects women two times more than men, but men have more aggressive types of MS. It is followed by unpredictable periods of remissions and relapses. After certain number of relapses and remissions, patients accumulate neural lesions, and it leads to disability.

Current Treatment of Multiple Sclerosis

Modern medicine has no cure for multiple sclerosis. Treatments are based on reducing the progress of the disease and management of the symptoms. Due to severity of the symptoms, in some cases there is no need for any kind of treatment.

There are three types of strategies for treatment of multiple sclerosis- treatment of attacks, slowing down of the progress and treatment of symptoms. Due to stage of disease, various drugs are used. For acute attacks glucocorticoids are used. Beta- interferons are used in modification of the multiple sclerosis course, and potassium blockers and oral vitamin D are used in treatment of the symptoms.

New Treatments of Multiple Sclerosis

There were many researches on mice, and they had encouraging results. First problem for scientist studies on mice was to find neural lesion similar to lesion in multiple sclerosis in human CNS. This problem was solved because they found out that lesions experimental autoimmune encephalomyelitis is identical to MS lesions in human CNS. These lesion were treated with stem cells, and they gave extraordinary results. Infiltrated stem cells gave gradual improvement in multiple sclerosis symptoms. This was just a beginning in treatment of multiple sclerosis with stem cells.

Therapy of MS with purified stem cells, isolated from bone marrow and umbilical cord blood, is promising way of treatment. These cells have been named CD 34+ cells. The CD 34+ cell can migrate to lesion location and there it can proliferate and differentiate in specific cell which can repair the damage. In case of multiple sclerosis, these cells transform in oligodendrocytes. This way of treatment is now under development, and we expect results as soon as possible.

Use of Various Stem Cells in Treatment of MS

Hematopoietic stem cell have been used in treatment of leukemia and other blood cancers. The bone marrow was transplanted in this process. Fortunately, scientist have discovered that this way of treatment is suitable for patients with very aggressive forms of multiple sclerosis. The procedure consists of destruction of patients immune system which has immune memory. When bone marrow is destructed, patient receives previously taken hematopoietic stem cells from himself, or from some other donor. Transplanted hematopoietic stem cells have no immune memory. Therefore, they should not have tendency of autoimmune destruction. However, this procedure is not used in treatment of every single patient with multiple sclerosis, because destruction of immune system carries certain dose of risk and possibility of fatal complication.

An ideal resource for treatment of MS with stem cells were neural stem cells. These cells were considered as very good way of filling destroyed loci with oligodendrocytes. This research showed a lot of promise, but it didn’t show expected results. Results were disappointing because, this way of treatment showed low level of oligodendrocytes renewal.

Future Possibilities of MS Treatment

Another type of cells are being tested, like precursors of oligodendrocytes. Application of cell cultures from laboratories is one of the strategies, but cells cultures should be placed in multiple regions of brain, and it is not easy goal to achieve. Another strategy is stimulation of remained brain oligodendrocyte precursors. These precursors would be transformed in oligodendrocytes and then these oligodendrocytes would migrate to demyelination loci and repair demyelinated neurons.

The Latest Discoveries in Stem Cell Treatment of MS

Scientists have discovered procedure which can convert human skin cells to neural cells. This revolutionary discovery can replace neurons in many neurodegenerative diseases like multiple sclerosis, but also in other myelin degenerative processes. In these neurodegenerative conditions myelin cells are destroyed, and they cannot be replaced. However, this newest research gives an opportunity of producing large quantities of myelinating cells which isolate communication between two neural cells. Basically, skin fibroblasts, very common cells in human skin, are converted into oligodendrocytes. This process includes reprogramming of the cell. Scientists have exchanged structure of three protein types, and that induced fibroblast to change into oligodendrocyte precursors.
Research team developed billions of induced oligodendrocytes progenitor cells in short time, and, more important thing, they have showed that these cells gave significantly improvement in reparation of oligodendrocytes in mice.

In past, oligodendrocytes progenitor cells were produced only from embryonic stem cells, and this method had some limitations. The main limitation was disability to produce quick and stabile amount of oligodendrocytes, but with new method this difficulty became past. If this method shows good results on human trials, it could be common treatment for many people with myelin disorders.

Another recent study focuses on glial progenitor cells. These cells can differentiate in astrocytes and oligodendrocytes. However, this progenitor cells stop dividing themselves or even they differentiate into specialized cells, and this is the main obstacle in further research. Scientist have found out that the main role in cell division plays beta-catenin and it is regulated by glycogen synthase kinase 3 beta(GSK3B). If researchers only could block this synthase (because this GSK3B is being blocked during cell division), they would solve this problem with early differentiation.

Summary

According to these researches, MS could be stopped or even cured if at least one of these researches succeeds in their attention. Stem cells have showed that they present future in modern medicine, and it's all up to scientists to find out the best way of curing these harmful diseases.
#2
Multiple sclerosis and stem cells

The original article in this thread summarises ways in which different stem cell therapies are being tested for multiple sclerosis (MS), particularly in animal models. The research in this area is particularly driven by the need to develop therapies for aggressive MS that has proven unresponsive to other existing therapies. It is considered to be a promising means of intervention in such cases, but caution is needed as there are some safety concerns.

Autologous haematopoietic stem cell transplantation has been tried in various countries, including the Czech Republic, Italy and China in both single-centre and multi-centre trials. In Italy, patients were treated with an intermediate intensity conditioning regimen, named BEAM/ATG. Observations on patients treated between the years 1996-2008. Study of outcomes for these patients suggested that the regimen helped suppress or slow disease progression and caused sustained clinical improvement in patients who were unresponsive to conventional therapies. The Czech experience with patients with aggressive, unresponsive MS at a single centre was similar. Both countries reported that the stem cell treatment was especially beneficial in patients in the relapsing-remitting phase of the disease. A retrospective analysis of outcomes in 25 MS patients in a single centre in China similarly reported that autologous haematopoietic stem cell transplantation is a feasible treatment for severe MS with good long-term efficacy. Studies on phenotype and function of peripheral blood lymphocytes from MS patients undergoing a trial of myeloablative autologous haematopoietic stem cell transplantation suggests that the transplantation favourably modifies the balance of regulatory and pro-inflammatory lymphocytes to allow suppression of central nervous system inflammation.

However, caution is necessary when deciding whether or not to use autologous haematopoietic stem cell transplantation. Some of the studies mentioned reported major early toxicity and deaths directly due to the transplants. A case study from Costa Rica of a 17-eyar old girl who underwent stem cell transplantation nine months after being diagnosed with MS reported that she suffered life-threatening encephalomyelitis as a result of the therapy, although she eventually recovered. The therapy is still experimental at this stage and more development with formal, controlled clinical trials is necessary before it could be more generally introduced as a therapy for MS. Such trials are currently underway.

Sources

ALDERAZI, Y.J., COONS, S.W. and CHAPMAN, K., 2012. Catastrophic demyelinating encephalomyelitis after intrathecal and intravenous stem cell transplantation in a patient with multiple sclerosis. Journal of child neurology, 27(5), pp. 632-635

CHEN, B. et al., 2012. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurological Sciences: Official Journal Of The Italian Neurological Society And Of The Italian Society Of Clinical Neurophysiology, 33(4), pp. 881-886

KRASULOVÁ, E. et al., 2010. High-dose immunoablation with autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a single centre 10-year experience. Multiple sclerosis (Houndmills, Basingstoke, England), 16(6), pp. 685-693

MANCARDI, G.L. et al., 2012. Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience. Multiple sclerosis (Houndmills, Basingstoke, England), 18(6), pp. 835-842

PATANI, R. and CHANDRAN, S., 2012. Experimental and therapeutic opportunities for stem cells in multiple sclerosis. International Journal Of Molecular Sciences, 13(11), pp. 14470-14491

SACCARDI, R. et al., 2012. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Multiple sclerosis (Houndmills, Basingstoke, England), 18(6), pp. 825-834
  

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