Mice Pave the Way to Insights About Sickle Cell Anemia Sickle cell anemia (1) affects the shape, function, and longevity of the red blood cells that carry oxygen to your tissues. The problem is caused by a genetic defect in one of the genes that encodes hemoglobin, the protein that ferries the oxygen around. Although people who carry this sickle cell mutation are somewhat protected from malaria, those who have two copies of the mutation suffer the pain and debilitation associated with deficient and disrupted blood supply. Current treatments for the disease include treating the symptoms or trying to reactivate a different hemoglobin gene that is usually shut off at early development. A more permanent solution, however, could lie in supplying the body with the sort of stem cells that can make blood, but in this case cells that synthesize the normal kind of hemoglobin, not the defective version. Research by Hanna et al. (2) have shown the way towards just this sort of treatment. Although these results are still a long way from application to people in a medical setting, their results with mice are nonetheless promising. These authors began with skin cells from a mouse and added in four genes already known to induce cells toward a pluripotent state. The resulting cells, called induced Pluripotent Stem (iPS) cells, although not derived from embryos, resemble embryonic stem cells in their functionality (3). Addition of another key protein then sent these cells down the pathway toward becoming blood cell precursors that were capable of replacing the blood system of another mouse. To apply this approach to sickle cell anemia, the authors began with mice that had their own hemoglobin genes replaced with human hemoglobin genes of the mutated, sickle-cell type. The skin cells of these mutant mice also carried the genetic defect. The authors applied their protocol to derive iPS cells from the skin cells, then used gene therapy to fix the mutation in the hemoglobin genes. They went on to derive blood cell precursors from the iPS cells. When these same blood cell precursors, with their genes fixed, were put into mice that still had the mutant sickle cell trait, their blood functioned in a much more normal fashion, and the condition of the mice was much improved. Although this work was in mice, and the only human components were a few genes, still, the work provides a proof of principle showing how cells derived from a bit of skin could be tuned up, redirected, and returned to a patient to address the patient’s sickle cell anemia. Our optimism must be tempered with caution, however, as the procedures used in this experiment have the potential to generate unexpected tumors. Further analysis and refinement of the approach will be necessary to understand whether this experimental approach can eventually be applied to people. 1. See more information on Sickle Cell Anemia at MedLinePlus, from the National Institutes of Health. URL: http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html (accessed March 14, 2008). 2. Hanna, J., Wernig, M., Markoulaki, S., Sun, C. W., Meissner, A., Cassady, J. P., Beard, C., Brambrink, T., Wu, L. C., Townes, T. M., Jaenisch, R. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318, 1920-1923. 3. Read more on the background of iPS cells *Author affiliation Posted February 26, 2008
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