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Feb 15, 2010 (Vol. 30, No. 4)

Induced Pluripotent Stem Cell Overview

Review of Opportunities and Challenges in this Rapidly Expanding Field of Study

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    Having standards for iPS cells could help define the differences between these murine embryonic stem cells and their induced counterparts.

    The ability to reprogram somatic cells to generate induced pluripotent stem (iPS) cells has generated tremendous interest and discussion since iPS cells were first produced from mouse cells in 2006 and human cells in 2007.

    The reversion of differentiated cells to a state resembling embryonic stem cells offers a wealth of opportunities for disease researchers. Interest in iPS cells is expanding rapidly beyond the domain of stem cell experts to researchers modeling complex diseases in vitro and pursuing novel therapeutics.

    “With iPS cell technology, you can now take a skin biopsy from a patient with a genetic disease such as familial Alzheimer or Lou Gehrig disease and turn their somatic cells into stem cells,” explains Chad Cowan, Ph.D., of the Harvard Stem Cell Institute. “You can then take those stem cells and turn them into cell types that might be affected in the disease.”

    Along with the opportunities offered by iPS cells, practical challenges still abound. Culturing stem cells relies on both science and art and defining just what exactly constitutes a stem or iPS cell is stimulating a good deal of discussion.

  • Disease Modeling

    Dr. Cowan’s lab is using iPS cells to support studies of obesity and metabolic disorders. While the lab can easily obtain fat cells from patients, these cells can’t be cultured over the long term. “We can keep the fat cells alive for a short period of time but that only allows us to do a one-time endpoint assay. It doesn’t allow us to tease out the complexities of what might be going wrong in a patient with a metabolic disorder. The ability to make patient-specific fat cells from iPS cells completely changes the game.”

    With iPS cells, the lab can conduct dozens of assays to identify differences in fat cells from a person with a metabolic disorder such as type 2 diabetes versus a person with normal body weight or someone without diabetes. The ability to take a single genotype and potentially make any of the tissues that might be involved in a metabolic disorder such as hypothalamus, pancreatic beta cells, and hepatocytes, could lead to powerful disease models.

    In his lab at the University of California, Santa Barbara, Dennis Clegg, Ph.D., is using iPS cells as one tool to study the loss of vision in age-related macular degeneration (AMD). In AMD, the degeneration of retinal pigment epithelial (RPE) cells appears to cause the death of neighboring rods and cones in the macular region of the central retina.

    Dr. Clegg’s lab is evaluating the use of iPS-derived RPE cells to treat AMD and using iPS cell lines to create ocular cells, which can be used to study how the eye develops. “The real utility of iPS cells is that you can study human cells and processes in ways you couldn’t do before,” notes Dr. Clegg.

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