Isolation of pure neuronal cell lines from stem cells, their survival, and the risk of tumor formation following transplantation in the brain, have been some of the major issues plaguing stem cell research aimed at treating neurological diseases and disorders. A new study, published in the recent issue of The Journal of Neuroscience, reports the possibility of treating neurodegenerative disorders by transplanting neuronal cells obtained from genetically modified embryonic stem cells (ESCs).
A team of researchers, led by Stuart A. Lipton, Director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at the Burnham Institute for Medical Research, California, report that they have developed transformed murine embryonic stem cells that express a calcium-dependent transcription factor, myocyte enhancer factor 2C (MEF2C). MEF2C, belonging to the family of MCM1agamous-deficiens-serum response factors (MADS), is associated with cardiomyocyte differentiation, and the survival and synapse formation of the neurons. The scientists established that the expression of MEF2C also enhances the production of neuronal progenitor cells capable of differentiating into almost pure cultures of neurons that could survive, averting apoptosis, in the brain without tumor formation. In order to establish whether the new neurons are incorporated into the brain network of the mouse model, they conducted electrophysiological studies and demonstrated that the new stem cell-derived neurons could effectively conduct electrical signals to other parts of the brain. In addition, neurobehavioral tests conducted to determine the cognitive effects of the new cells, showed a significant improvement in stroke-induced behavioral deficits.
Several stem cell based studies have been conducted to establish a potential treatment for common neurological disorders, although it is not yet proven that stem cells can ameliorate the dysfunction (memory dysfunction) associated with such diseases. To study the effects of stem cells on memory dysfunction, Yamasaki and colleagues (The Journal of Neuroscience, 2007) generated a transgenic mouse model, in which the expression of diphtheria toxin A chain was regulated by the tetracycline-off system. The scientists observed neuronal loss in the hippocampus that led to specific destruction of memory. They also found that neural stem cells, after transplantation in the brain, could survive, migrate, differentiate, and significantly enhance memory in the mouse model. Based on the findings, the researchers suggested therapeutic application of stem cells in diseases and disorders that lead to memory loss.
Brain conditions like stroke, ischemia, brain injury, and Alzheimer, Parkinson and Huntington diseases, lead to memory loss and other debilitating effects by disrupting the brain cells. According to statistical data presented by the American Stroke Association, approximately 780,000 people experience new or recurrent stroke annually. The Alzheimer’s Association has estimated that currently, over 5.2 million people have the disease in the US, and also speculate that 10 million people, born between 1946 and early 1960s, will develop the condition later in their lives.
Limitations for the use of stem cell transplants in the treatment of neurodegenerative diseases include the possibility of differentiation of the embryonic stem cells into glial cells without neuronal properties, apoptosis of the stem cell-derived neuronal cells after transplantation in the brain, and their occasional conversion into tumors. Theoretically, the transplant of neuronal brain cells could restore some of the brain function similar to the re-establishment of cardiac function after heart transplantation. The novel study in mouse models demonstrating effective neuronal transplantation in the brain could be a major breakthrough in stem cell therapy for neurodegenerative disorders including Alzheimer, Parkinson, and Huntington disease.
About Burnham Institute for Medical Research – A nonprofit, public benefit corporation, headquartered at La Jolla, California, it is one of the fastest growing research institutes, ranking among the top four private research institutes in the US to receive National Institutes of Health (NIH) grants. The institute is acknowledged for its outstanding competency in stem cell research and drug discovery technologies, with various research programs in the fields of neurodegenerative disorders, cancer, diabetes, infectious diseases, inflammatory diseases, and childhood diseases.
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