January 16, 2025
Our research focus is to develop stem cell therapies for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and ALS.
We reported that human fetal neural stem cells transplanted into 24-month-old rats developed into neural cells and significantly improved the cognitive function of the animals. However, ethical and technical issues put off the clinical use of fetal or embryonic stem cell. Recently we succeeded to produce neural cells form adult human mesenchimal stem cells after modification of DNA methylation. Currently, we are investigating genes, which regulate stemness to convert committed cells into pluripotent cells. We also one-step further to extend this autologous cell therapy concept by a small molecule compound. Peripheral administrations of this compund not only dramatically (7 fold) increases endogenous neural stem cell but also neurogenesis in the aged rats.
Investigation of stem cell biology also give us a clue for cause of disease. We found reelin, which expression is known to be reduced in schizophrenia and autism, and ?-amyloid precursor protein (APP), which produces amyloid ? depositions in Alzheimer’s disease, are involved in stem cell migration and differentiation using knockout and/or transgenic mice. Thus these factors may play an important role not only in neuroplasticity in the normal condition, but also in a deficit of adult neurogenesis under pathological conditions. Thus we are investigating novel therapeutic strategies for this disease, including modifications of stem cell and regulation of these factors.
Using all these advanced stem cell technologies, we may be able to change therapeutic strategies for neurodegenerative diseases form delaying progress of the diseases or symptomatic treatments to the cure near future. Our researches are supported by NIH (R01 AG 23472 and R01AG20011) and Alzheimer’s Association (IIRG-03-5577).
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