Sickle-Cell Breakthrough Shows Great Promise of iPS Cells

Mouse containing cells derived from
a reprogrammed fibroblast. Image: Sam Ogden.

Researchers recently cured sickle-cell anemia in a mouse model using iPS cells, highlighting the promise of iPS cells for future research and affirming the importance of preventing the current excitement about iPS cells from hastily ending embryonic stem cell research.

George Q. Daley, a stem cell researcher at Children’s Hospital Boston explains, “I think it is a really exciting proof-of-principle that clinical applications of iPS cells are technically feasible, [however], there will be lots of unanticipated setbacks before we end up in the clinic.” The study suggests significant promise for application in humans with time and further research.

Researchers used a mouse model developed by Tim Townes, in which they replaced the genes responsible for producing mouse hemoglobin with genes coding for the hemoglobin structure normally found in humans with the sickle cell phenotype. The experiment involved reprogramming mouse skin cells with retroviruses to produce the iPS cells, correcting the sickle-cell mutation in these cells using homologous recombination, differentiating these cells into blood-producing stem cells, and then transplanting the blood-producing stem cells into the mouse from which they were derived. After transplanting these cells into the mouse, it soon began producing healthy blood cells.

The use of iPS cells alleviated concerns associated with embryonic stem cell research, such as administering immunosuppressant drugs to prevent rejection of unmatched transplanted cells. Investigator Rudolph Jaenisch noted: “This demonstrates that iPS cells have the same potential for therapy as embryonic stem cells, without the ethical and practical issues raised in creating embryonic stem cells.” The study claims that the outcome opens the opportunity to repair genetic defects through homologous recombination and to repeatedly differentiate iPS cells into desired cell types for therapeutic applications. Jaenisch’s lab chose sickle cell anemia given its simple cause, and is now developing techniques to treat other diseases using the same method. Though if these new techniques succeed in humans, experts anticipate FDA approval of personalized treatments to take a long time.

Notwithstanding this breakthrough, many obstacles stand in the way of human application. Among them: bypassing the use of genes known to cause tumors as inducers of cellular reprogramming, avoiding the use of retroviral vectors which pose the risk of unintentional changes to an organism’s genes, and improving methods for human iPS differentiation. Jaenisch acknowledged that, “the big issue is how to replace these viruses.”

Despite this success, scientists need a greater understanding of how the iPS cells work before considering a step away from embryonic stem cell research. With the Bush administration’s advocacy for non-embryonic stem cell research and their celebration of the development of human iPS cells, they will naturally present this development as further encouragement to stop embryonic stem cell research. Representative Diana DeGette (D-CO), who championed the Stem Cell Research Enhancement Act (H.R.3, S.5) explains that pitting iPS research against the embryonic research is the wrong approach: “None of this feels like it should be one versus the other…That’s the politicization of science.”

Tags: stem cells

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