Stem cells in drug screening for neurodegenerative disease

Abstract

Because the average human life span has recently increased, the number of patients who are diagnosed with neurodegenerative diseases has escalated. Recent advances in stem cell research have given us access to unlimited numbers of multi-potent or pluripotent cells for screening for new drugs for neurodegenerative diseases. Neural stem cells (NSCs) are a good model with which to screen effective drugs that increase neurogenesis. Recent technologies for human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) can provide human cells that harbour specific neurodegenerative disease. This article discusses the use of NSCs, ESCs and iPSCs for neurodegenerative drug screening and toxicity evaluation. In addition, we introduce drugs or natural products that are recently identified to affect the stem cell fate to generate neurons or glia.

Keywords: Drug screening; ES cells; IPS; Neurodegeneration; Stem cells.

Fig. 1

High-throughput screening for the development of new drugs that are effective for the treatment of neurodegenerative diseases. NSC can be derived from adult cells, fetus cells, ESCs or iPSCs. After NSC plating, chemical or natural product libraries are treated. The effect of each drugs are detected by immunocytochemistry using cell type specific antibodies. If fluorescence conjugated secondary antibodies are used, cells can be visualized by fluorescence microscopy and the numbers of detected/differentiated cells are counted. If HRP conjugated secondary antibodies are used, cells can be treated with substrates and lysed to be measured by microplate reader. Once the chemicals or natural products that are effective are found, and structural activity relationship studies, animal studies and toxicity evaluations are done, promising agents can go on to clinical trials and may further be developed as new drugs.