Japan is spending substantial amounts of money in several projects aimed at using pluripotent stem cells in the clinic.

Japanese education minister Hakubun Shimomura recently unveiled a plan to spend 110 billion yen over the next decade to promote regenerative medicine using iPS cell technology. He unveiled the plan at a meeting with Kyoto University professor Shinya Yamanaka, who won the Nobel Prize in medicine last year for his advanced research on iPS cells that can grow into any type of body tissue.

“It’s now our duty as researchers to (seriously) take this assistance and truly move forward (in iPS-related research),” Yamanaka said.

One such projects is to stockpile artificially derived stem cells for clinical research is intended to create induced pluripotent stem cells from the blood of people with rare cell forms, known as the HLA type, that are less prone to rejection by the immune system when transplanted.

The cells will be stockpiled for immediate use, saving considerable time and money that would otherwise be needed to create iPS cells from cells from the patient.

The Kyoto University’s Center for iPS Cell Research and Application said it has gained the consent of people with those rare cells to collect enough blood to produce cells for transplants for around 20 per cent of the Japanese population, with limited risk of immune rejection. Up to 80 per cent of the population can be covered if people with 75 varieties of special cells are found.

A projects is also lead by the co-winner of the 2012 Nobel Prize in physiology or medicine for the discovery that mature cells can be reprogrammed to become any part of the body for transplant, looks at treating Parkinson's disease. This is three years away from clinical trials. Another method, by the institute RIKEN, to treat muscular degeneration should start trials next year.

By 2020, Yamanaka hopes to develop 75 standard cell lines that could be used to treat 80 per cent of the population. By then, there would be plenty of clinical trials or even a commercial therapy using pluripotent cells.

Prime Minister Shinzo Abe has presented a letter of appreciation to Shinya Yamanaka for his research on induced pluripotent stem cells, which have the potential to grow into any type of body tissue.

Shinya Yamanaka and John Gurdon, two leading lights of stem-cell research won last year’s Nobel Prize in Physiology or Medicine for the discovery that cells can be reprogrammed to an embryonic-like state. It has been hailed as a new dawn for regenerative medicine.

They discovered that a mature, adult cell can be turned back to an infant, versatile state called a stem cell. The discovery has revolutionized our understanding of how cells and organisms develop.

In 1962, John Gurdon replaced the cell nucleus of a tadpole embryo with that of an adult. The embryo developed normally, showing that the DNA of the adult cell retains the ability to develop into another adult.

Shinya Yamanaka in 2006 went a step further. He took adult mouse skin cells and reprogrammed them into becoming young again. He also showed that this reprogramming required the tweaking of just four genes.

While in 1962 Gurdon worked out that cells could be reprogrammed into a more immature state , in 2006, Yamanaka worked out how to turn mature cells in mice into stem cells by introducing a few genes. Yamanaka’s 'induced pluripotent stem cells' removed the need to use live human embryos to create versatile stem cells.

Their work has together laid the foundations of regenerative medicine, where we could take adult cells of a patient and re-programme them into growing into any tissue.

Reprogrammed cells regain pluripotency, the potential to differentiate into many mature cell types. Many researchers hope that cells created in this way will eventually be used in regenerative medicine, providing replacement tissue for damaged or diseased organs.

In 2009, scientists at the Scripps Institute in California demonstrated methods to produce pluripotent cells using proteins without tweaking the DNA.

Their discoveries concern the manipulation of living cells, and lie at the heart of the techniques for cloning animals and generating stem cells, the primitive cells from which the mature tissues of the body develop.

Gurdon was the first person to demonstrate that cells could be reprogrammed, in work published 50 years ago. At the time, scientists believed that cellular specialization was a one-way process that could not be reversed. Gurdon overturned that dogma by removing the nucleus from a frog egg cell and replacing it with the nucleus from a tadpole’s intestinal cell. Remarkably, the process was able to turn back the cellular clock of the substitute nucleus. Although it had already committed to specialization, inside the egg cell it acted like an egg’s nucleus and directed the development of a normal tadpole.

Gurdon was a graduate student at the University of Oxford, UK, when he did the work. He received his doctorate in 1960 and went on to do a postdoc at the California Institute of Technology in Pasadena, leaving his frogs in Europe. He did not publish the research until two years after he got his PhD, once he was sure that the animals had matured healthily.

Mammalian cells did not prove as amenable to this process, known as cloning by nuclear transfer, as frog cells. It was nearly 35 years before the first cloned mammal — Dolly the sheep — was born, in 1996. Dolly was the only live birth from 277 attempts, and mammalian cloning remained a hit-and-miss affair.

Scientists were desperate to improve the efficiency of the system and to understand the exact molecular process involved. That is where Shinya Yamanaka made his mark. Yamanaka used cultured mouse cells to identify the genes that kept embryonic cells immature, and then tested whether any of these genes could reprogram mature cells to make them pluripotent.

In the mid-2000s, the stem-cell community knew that Yamanaka was close. A few months later, attendees at the 2006 meeting of the International Society for Stem Cell Research in Toronto, Canada, packed out Yamanaka’s lecture. The audience waited in silence before he announced his surprisingly simple recipe: activating just four genes was enough to turn adult cells called fibroblasts back into pluripotent stem cells. Such induced pluripotent stem (iPS) cells could then be coaxed into different types of mature cell types, including nerve and heart cells.

The techniques they developed reach to the beginnings of life, and have generated objections from people who fear, on ethical or religious grounds, that scientists are pressing too far into nature’s mysteries and the ability to create life artificially.

Dr. Gurdon’s discovery came in 1962, when he produced living tadpoles from the adult cells of a frog. His work was at first greeted with scepticism, because it contradicted the textbook dogma that adult cells are irrevocably assigned to their specific functions and cannot assume new ones. (His prize was the first Nobel to be awarded to a cloner.)

Dr. Gurdon’s technique was to extract the cell nucleus, containing the frog’s DNA, from a mature intestinal cell and inject the nucleus into a frog egg whose own nucleus had been removed. The egg was evidently able to reprogram the introduced nucleus and direct its genes to switch from the duties of an intestinal cell to those appropriate to a developing egg.

But how did the egg cell body accomplish this reprogramming feat? The answer had to wait 44 years, while molecular biologists gained a more intimate understanding of genes and the agents that control them.

Working with mice, Dr. Yamanaka discovered in 2006 that the reprogramming can be accomplished by just four specific gene control agents in the egg. The agents, known to biologists as transcription factors, are proteins made by master genes to regulate other genes. By injecting the four agents into an adult cell, Dr. Yamanaka showed that he could walk the cell back to its primitive, or stem cell, form.

Stem cells generated by this method, known as induced pluripotent cells, or iPS cells, could then be made to mature into any type of adult cell in the body, a finding with obvious potential for medical benefits.

Biologists hope the technique will enable replacement tissues to be generated from a patient’s own cells for use against a wide variety of degenerative diseases. For the moment, that remains a distant prospect. But the cells have already proved useful in studying the genesis of disease. Cells generated from a patient are driven to form the tissue that is diseased, enabling biologists in some cases to track the steps by which the disease is developed.

The two developments led to the concept of therapeutic cloning — take a patient’s skin cell, say, insert it into an unfertilized human egg so as to reprogram it back to pluripotent state, and then develop embryonic stem cells for conversion into the tissue or organ that the patient needed to have replaced. Since the new tissue would carry the patient’s own genome, there should be no problem of immune rejection.

But human eggs are not so easily obtained. Of course, the reprogramming might be accomplished without human eggs if only the relevant factors in the egg could be isolated. But that seemed a distant prospect until Dr. Yamanaka’s discovery that 24 transcription factors, later whittled down to four, could reprogram a nucleus when introduced into cells on the back of a virus.