New Tools to Study Disease
Rodney Rietze, PhD*

Two major approaches in stem cell-based therapeutics focus on the utilization of the patients’ resident stem cells, or the generation of patient-specific stem cells in the culture dish, providing an unlimited supply of cells that have been lost or damaged, as part of the disease process. Tremendous progress has recently been made in relation to the latter strategy, with the discovery of induced human pluripotent stem cells (iPS) by Yamanaka in 20071. This technology enables the transformation of skin cells via specialised viral infection into stem cells (See Stem Cell Briefing).

Immediately researchers envisioned a means not only to generate an unlimited supply of patient-specific cells for transplantation, but also to generate human stem cell lines, which can be used to understand complex human conditions such as Lou Gehrig’s disease (ALS, amyotrophic lateral sclerosis) or Alzheimer’s Disease. Two recent advances now provide further evidence of the feasibility of such iPS cell-based approaches, and highlight the rapid progress being made on this front.

In the first paper, Dimos and colleagues2 tackle the important question of whether age, or disease progression alters the ability of skin cells to be reprogrammed into stem cells using the iPS strategy.  This was addressed by taking skin cells from elderly sisters (82 and 89 years of age respectively) suffering from ALS but with very different disease severity. By utilising the Yamanaka methodology of virally infecting skin cells with four critical factors the group was able to successfully generate iPS cells in both cases. The investigators also coaxed these newly generated iPS cells to form motor neurons, the population of cells that are affected during the progression of ALS.  These results now demonstrate that it is indeed possible to take tissue from a disease-affected patient, create iPS cell lines and then generate a limitless supply of the affected cell population.

In a related work, Park and colleagues3 extend these findings by successfully generating iPS cell lines from individuals with a variety of diseases including but not limited to Down syndrome, Parkinson’s disease, Huntington’s disease and type-1 diabetes using the same methodology as described above. The generation of a cohort of iPS cell lines from patients (a total of 10 lines were generated) not only enables a detailed investigation of how a disease affects particular cells, but also an opportunity to repair the gene defects in the culture dish.

These advances now provide investigators a means to more faithfully recapitulate complex human conditions ex vivo, and allow a level of interrogation at the molecular level not previously possible.

*Author Affiliation
Rodney Rietze, PhD
Queensland Brain Insititute
University of Queensland
Brisbane, Australia

Notes

1. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., and Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872.

2. Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., Croft, G. F., Saphier, G., Leibel, R., Goland, R., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321, 1218-1221.

3. Park, I. H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M. W., Cowan, C., Hochedlinger, K., and Daley, G. Q. (2008). Disease-specific induced pluripotent stem cells. Cell 134, 877-886.

Posted October 15, 2008