THE LIMITS OF STEM CELLS
They’re endlessly adaptable, but it turns out some of those adaptations are dangerous,
In 2001, U.S. President George W. Bush banned federal funding for new sources of stem cells developed from preimplantation human embryos. The action stalled research and discouraged scientists.
Five years later, a Kyoto University scientist, Shinya Yamanaka, and his graduate student, Kazutoshi Takahashi, re-energized the field by devising a technique to “reprogram” any adult cell, such as a skin cell, and coax it back to its earliest “pluripotent” stage. From there it can become any type of cell, from a heart muscle cell to a neuron.
The breakthrough sidestepped the embryo controversy, offering researchers an unlimited supply of stem cells. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for reprogramming mature cells into what are now called induced pluripotent stem cells, or iPS cells. Still, the march toward new treatments has been halting.
Yamanaka directs Kyoto University’s Center for iPS Cell Research and Application.
There has been great enthusiasm and confidence for nearly 20 years that the use of stem cells will lead to powerful new treatments for a range of diseases. Now, 10 years after your discovery, what treatments have been developed?
We are still in the early stages. In 2014, Dr. Masayo Takahashi and her colleagues at the Riken Center for Developmental Biology had great success using iPS cells to treat macular degeneration.
They took skin cells from a 70-year-old patient and derived iPS cells from them. They then differentiated the stem cells (directed them “back down” the normal developmental path) to become adult retinal cells. These were transplanted into the patient’s eye to treat the disease. That was a huge success. She sees much better now.
Have more patients been treated?
Before the transplantation for the second patient, we checked the genome sequence of the patient’s iPS cells and we identified a mutation in the cells. So we did not proceed.
The pluripotent stem cells (have the) ability to proliferate rapidly and infinitely. But it’s a double-edged sword. After multiple cell cycles, the chances of mutations increase. This could include mutation to produce an oncogene that can cause cancer.
So these treatments are now on hold?
Yes. We are developing allogenic stem cell lines — stem cells from donors. They would not be the patient’s own, but compatible cells to transplant into the patient, much like blood transfusions with compatible blood types.
How many compatible donor cell lines do you expect will be needed to cover the Japanese population?
Not that many. One particular line — just one — can work for 17 per cent of the Japanese population. We estimate that altogether about 100 lines will suffice for the 100 million people in Japan.
How many lines would be needed for the more diverse U.S. population?
We would need only about 200 lines.
Was the promise of stem cells overstated?
In some ways, yes, it is overstated. For example, target diseases for cell therapy are limited. There are about 10: Parkinson’s, retinal and corneal diseases, heart and liver failure, diabetes and only a few more — spinal cord injury, joint disorders and some blood disorders. But maybe that’s all.
Why so few?
We have more than 200 types of cells in our body. But the diseases I described are caused by loss of function of just one type of cell. Parkinson’s disease is caused by failure of very specialized brain cells that produce dopamine. Heart failure is caused by loss of function of cardiac heart cell.
So, that’s the key. We can make that one type of cell from stem cells in a large amount, and by transplanting those cells, we should be able to rescue the patient. But many other diseases are caused by multiple types of cell failures, and we cannot treat them with stem cell therapy.
What are your biggest concerns about the future of stem cell treatments?
I think the science has moved too far ahead of talk of ethical issues. When we succeeded in making iPS cells, we thought, wow, we can now overcome ethical issues of using embryos to make stem cell lines.
But soon after, we realized we are making new ethical issues. We can make a human kidney or human pancreas in pigs if human iPS cells are injected into the embryo. But how much can we do those things?
It is very controversial. These treatments may help thousands of people. So getting an ethical consensus is extremely important.