Reprogramming allows us to turn any cell of the body into a stem cell. This discovery surprised many scientists and changed the way they think about how cells develop. Does the new technology also change ethical discussions about stem cell research? What new questions does it raise?
iPS cells were first made in 2006, only 8 years after the first human embryonic stem cells were grown in the lab.
Growing cells for therapies will require specialist systems and centres, so access to therapies may be limited to areas with suitable facilities
In 2006, Shinya Yamanaka showed that skin cells can be ’reprogrammed’ into stem cells. Like embryonic stem cells, these lab-grown ’induced pluripotent stem cells’ or iPS cells can make all the different cells found in the body. This discovery has led some people to argue that research on human embyronic stem cells is no longer necessary, and that human iPS cells solve the ethical dilemma posed by human embryonic stem research. But many questions remain about how reprogramming works. Most scientists think more research is needed to establish how similar or different iPS cells and embryonic stem cells really are.
Can we decide today whether iPS cells could or should replace embryonic stem cells? And would using only iPS cells resolve all ethical dilemmas about this research? To answer these questions, we need to consider both current scientific understanding and moral aspects of the issues: Are there any ethically relevant differences between iPS cells and embryonic stem cells?
Many scientific questions remain about both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). There is considerable disagreement among scientists about how these two types of cells may compare in terms of safety and likely effectiveness (‘efficacy’) in future cell therapies.
As with organ transplants, cells transplanted into the body may be rejected by the patient’s immune system. Since hiPSCs can be made from the patient’s own cells, e.g. skin cells, it is hoped that reprogramming can provide a source of patient-specific specialized cells that would be recognized by the patient’s body and would not be rejected. However, producing tailor-made cells to treat individual patients would be a time-consuming, slow process and is likely to be costly. Many scientists believe it is more likely that large banks of cells with different immune properties will be created so that acceptable matches can be found for most patients. These cell banks could contain cells made from hESCs or hiPSCs.
Safety standards for cells used in patients
The first clinical trials using hESCs are just beginning, focussed on eye disorders. No iPS cells have yet been grown at ‘clinical grade’ – the quality standard required for use in patients.
Both hESCs and hiPSCs can self-renew (copy themselves) indefinitely and this property must be turned off to prevent tumours from forming. In addition, the reprogramming techniques involve manipulating the genes inside the cells and hiPSCs may also be affected by the age of the cells they are made from. These issues pose challenges for scientists attempting to grow cells with controlled characteristics for use in patients. Some solutions have been proposed for such problems but further research is needed to assess all the effects of the reprogramming process and produce hiPSCs suitable for clinical use. Since the cells are patient specific, standardization will be a challenge. This means it is likely to be some time before reprogrammed cells will be approved for use in patients by regulatory bodies such as the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in the USA.
The safety and efficacy of hESC- or hiPSC-based therapies are complex issues, and it is not yet possible to draw any conclusions about whether one of these cell types is safer or more valuable for therapeutic use than the other. In both cases, more work is needed to fully understand how the cells behave and how they can be controlled to produce the particular specialized types of cells needed for treating certain diseases.
An important ethical consideration is accessibility of any new stem-cell-based therapy. Who should these therapies be available to and when? Will they be available only to rich patients in developed countries, or will they also be accessible to those in developing countries who may not be in a position to pay for the treatment? It seems difficult to identify any clear differences between hESC- or hiPSC-based therapies in this respect. Some points to consider are:
Scientists have shown that iPSCs made from a mouse can be inserted into a mouse embryo, where they can contribute to the mouse as it grows. hiPSCs could also in theory be turned into sperm and egg cells and used to make a new embryo. Although this has not been done using human cells, some people argue that it is unacceptable to use any cells in research that have the potential to develop into a new life. If hESCs have a special moral status because they can contribute to a human embryo under appropriate conditions, then hiPSCs should have the same special moral status if they, too, can contribute to a human embryo. Some also think hiPSCs do not resolve the discussions about use of embryonic cells in research because iPS technology was developed based on knowledge obtained by studying hESCs - though the force of this argument is debated.
But if we assign hiPSCs a special moral status, then should we also give that moral status to the skin cells from which they were derived? Some argue that there is a difference between what a cell can be converted into using human technology, and what its ‘active potency’ or ability is under natural conditions. They argue it is the cell’s active potency that determines what the cell is. For example, simply because a house can be converted into a pile of rubbish by the action of a tornado does not eliminate the important differences between a house and a pile of rubbish.
Other, less debated differences between hESCs and hiPSCs concern their use as tools for drug testing and in disease studies, their possible application in reproductive medicine and the impact of hESC and hiPSC research on women. These areas do not constitute ethical dilemmas to the same extent as the issues above, although there is some scientific debate regarding which type of cells is more suitable as tools for drug testing and disease research.
There are still many scientific questions that need to be answered before any final judgement can be made about whether hiPSCs could or should eventually replace hESCs in research and future therapies. Most scientists agree that further research is needed on both types of cells in parallel.
The most contested differences between hESC- and hiPSC-based therapies concern patient safety, effectiveness for use in treatments, the possibilities of standardization, accessibility to large numbers of patients and ethical controversy about the moral status of the cells. All these issues are ethically relevant and none can yet be answered definitively. Research on both hESCs and hiPSCs is in rapid development and as the scientific picture develops, the moral implications of both scientific and ethical differences between these cells must be re-assessed.
Extended factsheet with a fuller discussion of the issues by Kristina Hug (pdf)
EuroStemCell factsheet on ethical issues surrounding use of embryos in research
EuroStemCell FAQ on embryonic stem cells and research
EuroStemCell factsheet on the science of embyronic stem cells
EuroStemCell factsheet on reprogramming and iPS cells
EuroStemCell summaries of regulations on stem cell research in Europe
Research paper on ethical questions in the iPS cell era by Kristina Hug
Do we still need research on human embyronic stem cells? Commentary by Austin Smith and Clare Blackburn
Lead image and ethics road sign © iStockphoto.com/marekuliasz and iStockphoto.com/ZargonDesign respectively. Fibroblast image by Tilo Kunath. Embyronic stem cells image © Jenny Nichols/Wellcome Images. iPS colony image by Daniela Evers from the Reconstructive
Neurobiloogy, University of Bonn. Other images © Wellcome Library, London.