This technique also offers the possibility of repairing disease-causing genetic mutations before reintroducing the new cells, an approach that has been used with the adult stem cells that naturally regenerate some tissues. Success has been limited, though, because those precursor cells are notoriously difficult to grow and manipulate outside the body.
Recent experiments in mice suggest that treating genetic disorders in this manner with iPSCs is indeed feasible. Specifically, Rudolf Jaenisch of the Massachusetts Institute of Technology showed in 2007 that iPSCs could cure sickle cell anemia in an animal. The disease results from a single genetic mutation that causes red blood cells to adopt a deformed crescentlike shape. In this proof-of-concept study, investigators first reprogrammed skin cells from the mice into iPSCs. They then replaced the disease-causing gene in the iPSCs with a healthy version and coaxed the “repaired” iPSCs into becoming blood-forming stem cells. After transplantation back into the anemic mice, the healthy precursors produced normal red blood cells. In principle, this method could be applied to any other disease in humans for which the underlying gene mutation is known.
The multimillion-dollar question is how long it might take before iPSCs can be used to treat people. For the reasons already outlined, safety and control are absolutely essential before any iPSC-derived cells could be tested in humans. Current strategies to push embryonic stem cells or iPSCs into fully differentiated mature cell types cannot yet efficiently eliminate the occasional immature stem cells that might seed a tumor. An example underscoring why this is such a problem comes from a recent experiment in transplanting iPSC-derived dopamine-making neurons, which are the cells lost in Parkinson’s patients, into rats suffering a version of the human disease. Although the rats clearly benefited from the engrafted cells, some of the animals also eventually developed teratomas in their brain.
In light of the fast pace of discoveries so far, however, it is optimistic but not unreasonable to estimate that such obstacles could be overcome in as little as 10 years, and transplantation of iPSC-derived cells might then be ready for human testing to begin. But iPSCs could well demonstrate their therapeutic value much sooner. The study and treatment of many tissue-
destroying diseases, such as type 1 diabetes, Alzheimer’s and Parkinson’s, are limited by scientists’ ability to obtain the affected tissues for study or to grow them in cultures for extended periods, and iPSCs could therefore be of enormous service in so-called disease modeling.
The idea is to derive iPSCs from affected patients’ skin or blood cells and then convert them into the cell types involved in the patients’ diseases. Both Clive N. Svendsen of the University of Wisconsin–Madison and Lorenz Studer of the Sloan-Kettering Institute recently derived iPSCs from the cells of patients with the devastating disorders smooth muscular atrophy and familial dysautonomia, respectively.* When the iPSCs were transformed into the cell types affected in each of those diseases, the cultured cells recapitulated the abnormalities just as they are seen in patients.
This process could allow researchers to study the development of a disease in a petri dish, with the advantage of having a potentially endless supply of new cells, because the original iPSCs can be maintained indefinitely. Ultimately, the goal of academic scientists as well as pharmaceutical companies is to use these petri dish models to better understand the disease process and identify novel drugs to treat the illness.
This extremely promising use of iPSCs is not far off at all. Indeed, when Svendsen and Studer exposed their cell cultures to experimental drugs in each study, the disease “symptoms” were partially alleviated in the cells. This principle can now be applied to many other disorders for which treatments do not yet exist, and unlike transplanting cells into individuals, the result may be the development of drugs from which millions could benefit.