Effie Apostolou & Konrad Hochedlinger
Induced pluripotent stem cells offer promise for patient-specific regenerative therapy. But a study now cautions that, even when immunologically matched, these cells can be rejected after transplantation.
In 2006, Takahashi and Yamanaka made a groundbreaking discovery. When they introduced four specific genes associated with embryonic development into adult mouse cells, the cells were reprogrammed to resemble embryonic stem cells (ES cells). They named these cells induced pluripotent stem cells (iPS cells). This approach does not require the destruction of embryos, and so assuaged the ethical concerns surrounding research on ES cells. What's more, researchers subsequently noted that the use of 'custom-made' adult cells derived from human iPS cells might ultimately allow the treatment of patients with debilitating degenerative disorders. Given that such cells' DNA is identical to that of the patient, it has been assumed — although never rigorously tested — that they wouldn't be attacked by the immune system. However, Zhao et al. show, in a mouse transplantation model, that some iPS cells are immunogenic, raising concerns about their therapeutic use.
Regardless of the answers to the outstanding questions, this and other recent studies reach one common conclusion: researchers must learn more about the mechanisms underlying cellular reprogramming and the inherent similarities and differences between ES cells and iPS cells. Only on careful examination of these issues can we know whether such differences pose an impediment to the potential therapeutic use of iPS cells, and how to address them. In any case, these findings should not affect the utility of iPS-cell technology for studying diseases and discovering drugs in vitro.
Nature Volume: 474, Pages: 165–166 Date published: 09 June 2011