Stem cells in the treatment of neurodegenerative diseases (5)
(Continued; the beginning of the article is here)
Amyotrophic lateral sclerosis and stem cells
Lateral amyotrophic sclerosis, also known as Lou Gehrig's disease, is a neurodegenerative disease affecting the spinal cord and brain stem, usually manifesting in adulthood. In this disease, the upper and lower motor neurons die, which leads to progressive paralysis [60]. The classic symptoms of the disease, including the death of motor neurons and progressive muscle atrophy, were described more than 150 years ago [50]. The average age of the first manifestation of the disease is 55 years, and the prognosis of life expectancy after diagnosis is 2-5 years [50]. The cause of amyotrophic lateral sclerosis is still unclear.
In 2006, Chi et al. [61] conducted a study to clarify the role of nerve progenitor cells in the development of a mouse model of the disease. At the same time, an interesting fact was revealed that the degeneration of motor neurons stimulates neurogenesis and proliferation of nerve progenitor cells [61]. In another study, Corti et al. [62] nerve stem cells expressing Lewis X (CD15, 3-fucosyl-N-acetyllactosamine, a carbohydrate molecule, one of the markers of neural stem cells) and chemokine receptors, small proteins that play an important role in the development of the nervous system, were transplanted into the spinal cord of mice with a simulated disease. Their main functions are to indicate the direction of movement of progenitor cells to their locations and to ensure the constant proliferation of these cells.
This slowed down the progress of the disease and increased the survival time of animals due to the integration of transplanted cells into the spinal cord [62]. The results of these studies suggest that neurotropic factors produced by transplanted cells protect neurons from death and enhance neurogenesis. Since astrocyte anomalies are one of the main signs of amyotrophic lateral sclerosis, replacement of pathologically altered glial cells with glial progenitor cells was proposed as therapy [63, 64].
Studies conducted by Maragakis et al. [63] and Rothstein et al. [64], demonstrated that in people with amyotrophic lateral sclerosis and in the corresponding animal models, there is a violation of the functioning of astrocytes. The authors have shown that transplanted glial progenitor cells not only survive in a diseased organism, but also differentiate into astrocytes and suppress microgliosis in the spinal cord of a mouse model of amyotrophic lateral sclerosis [64]. These data demonstrate the potential for astrocyte replacement to slow the focal death of neurons in amyotrophic lateral sclerosis [64].
The results of these preclinical animal studies are very promising and may be transformed into clinical methods in the near future. On the other hand, the replacement of dying motor neurons may cause certain contradictions, since it is unclear whether it is possible to transform patients' own cells into healthy motor neurons and whether they will survive in pathological conditions of the body. A recent study inspires optimism about the development of a method for the treatment of neurodegeneration in amyotrophic lateral sclerosis. Dimos et al. [65] successfully transformed into motor neurons induced pluripotent stem cells obtained from the cells of an 82-year-old patient with a family history of the disease.
In 2008, Mazzini et al. [66] published the results of a clinical experiment in which they transplanted autologous mesenchymal stem cells to patients with amyotrophic lateral sclerosis by injection into the spinal cord. The authors claim that, according to the results obtained, the clinical use of mesenchymal stem cells for the treatment of amyotrophic lateral sclerosis is safe and provides a slowdown in the deterioration of the indicators of the forced vital capacity of the lungs and the functional state of the body in some patients [66]. However, they note that the study was conducted with the participation of a small number of patients and to confirm the results, it is necessary to reproduce it on a larger sample [66]. The Mazzini group did repeat the experiment with more patients and published the results in 2010. Unfortunately, this study did not reveal significant changes in the progression of the disease, which were obtained during earlier work [67].
Ending: multiple sclerosis and stem cells; conclusions.
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30.03.2012