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Updated: October 8, 2012 16:44 IST

“Wide-ranging applications for pluripotent stem cells”

Special Correspondent
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Shinya Yamanaka, Centre for iPS Cell Research and Application, Japan delivering a lecture in Chennai on Thursday. Photo: V. Ganesan
The Hindu Shinya Yamanaka, Centre for iPS Cell Research and Application, Japan delivering a lecture in Chennai on Thursday. Photo: V. Ganesan

Many more diseases can be targeted, says expert

While applications of induced pluripotent stem cells in stem cell therapy may be limited to a few diseases, its applications in drug discovery are wide-ranging, and many more diseases can be targeted, Shinya Yamanaka, Director, Centre for iPS Cell Research and Application, Japan, has said.

The Japanese scientist, whose breakthrough was the creation of embryonic-like stem cells from adult skin cells, believes that the best chance for stem cell therapy lies in offering hope to those suffering from a few conditions, among them, macular disease, Type 1 Diabetes, and spinal cord injuries.

On the other hand, there were multiple possibilities with drug discovery for a range of diseases, and Prof. Yamanaka was hopeful that more scientists would continue to use iPS for studying this potential.

He currently serves as the Director of the Center for iPS Cell Research and Application and as Professor at the Institute for Frontier Medical Sciences at Kyoto University. He is also a Senior Investigator at the University of California, San Francisco (UCSF) - affiliated J. David Gladstone Institutes.

An invited speaker of the CellPress-TNQ India Distinguished Lectureship Series, co-sponsored by Cell Press and TNQ Books and Journals, Prof. Yamanaka spoke to a Chennai audience on Tuesday evening about those “immortal” cells, that he originally thought would take “forever” to create, but actually took only six years.

“My fixed vision for my research team was to re-programme adult cells to function like embryonic-like stem cells. I knew it could be done, but just didn't know how to do it,” Prof. Yamanaka said.

Embryonic stem cells are important because they are pluripotent, or possess the ability to differentiate into any other type of cell, and are capable of rapid proliferation. However, despite the immense possibilities of that, embryonic cells are a mixed blessing: there are issues with post-transplant rejection (since they cannot be used from a patient's own cells), and many countries of the world do not allow the use of human embryos.

Dr. Yamanaka's solution would scale these challenges if only he and his team could find a way to endow non-embryonic cells with those two key characteristics of embryonic stem cells.

In 2006, he and his team of young researchers — Yoshimi Tokuzawa, Kazutoshi Takahashi and Tomoko Ishisaka — were able to show that by introducing four factors into mouse skin cells, it was possible to generate ES-like mouse cells. The next year, they followed up that achievement, replicating the same strategy and converted human skin cells into iPS cells. “All we need is a small sample of skin (2-3millimetres) from the patient. This will be used to generate skin fibroblasts, and adding the factors, they can be converted to iPS cells. These cells can make any type of cell, including beating cardiac myocytes (heart cells), Prof.Yamanaka explained.

iPS cells hold out for humanity a lot of hope in curing diseases that have a single cell cause. Prominent among them are Lou Gehrig's Disease or Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease. Motor neurons degenerate and die, and no effective treatment exists thus far. One reason is that there have not been good disease models for ALS in humans. It is difficult to get motor neuron from human patients and motor neurons cannot divide.

“Now, iPS cells can proliferate and can be differentiated to make motor neurons in large numbers,” he explained. Already a scientist in Japan has clarified motor neuron cells from iPS. “We are hoping that in the near future we would be able to evolve drug candidates that will be useful for ALS patients.” Treatment of spinal cord injuries using iPS cells has showed good results in mice and monkey specimens, and it is likely that in two or three years, scientists will be ready to start treatment for humans.

Toxicology, or drug side effects, is another area where iPS cells can be of use. Testing drug candidates directly on patients can be extremely dangerous. However, iPS cells can be differentiated into the requisite cell type, and the drugs tested on them for reactions. And yet, as wonderful as they may seem, iPS cells do have drawbacks, and there are multiple challenges to be faced before the technology can be applied to medicine. Are they equivalent and indistinguishable from ES cells? For a technology that has been around for only five years, the questions remain about safety. Also to derive patient-specific iPS cells, the process is time, and money-consuming, Prof. Yamanaka pointed out.

There are however, solutions in the offing, for the man who made the world's jaw drop with his discovery. One would be to create an iPS cell bank, where iPS cells could be created in advance from healthy volunteers donating peripheral blood, and skin fibroblasts, apart from frozen cord blood. The process of setting a rigorous quality control mechanism to select the best and safest iPS clones is on and would be complete within a year or two. “Many scientists are studying iPS cells across the world, and I'm optimistic that because of these efforts, we can overcome the challenges of iPS, and contribute to newer treatments for intractable diseases,” Prof. Yamanaka said.

N. Ram, Director, Kasturi & Sons Limited, introduced the speaker. Mariam Ram, managing director, TNQ India; and Emilie Marcus, executive editor, Cell Press, spoke.

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