With the hope of growing small blood vessels and restoring circulation in the legs, two patients were the first to be treated by transplanting a purified form of the subjects’ own adult stem cells into the leg muscles. Both patients suffered from severely blocked arteries and faced possible leg amputations. This first U.S. trial of the technique that has worked on laboratory animals was conducted by Northwestern University Feinberg School of Medicine.

“They’re at the end of the therapeutic road and they’re ultimately facing potential amputation,” said Douglas Losordo, M.D., the Eileen M. Foell Professor of Heart Research and principal national investigator for the study. “This is hopefully a way to help them avoid that.”

Losordo is director of the university’s Feinberg Cardiovascular Research Institute and director of cardiovascular regenerative medicine at Northwestern Memorial Hospital.

“The stem cells themselves can assemble into blood vessels,” Losordo said. “They can also secrete growth factors that stimulate and recruit other stem cells to come into the tissue and help with the repair. It’s an amazing biology we’re trying to leverage in these folks.”

The approach has proven to be effective in mice and rats during pre-clinical studies where stem cells were transplanted into the limbs of the animals.

“Based on that, we think it has a good chance of helping humans,” Losordo noted.

“This is a dreadful disease in which the profession has failed to offer much in the way of relief for these patients,” Losordo said. “We’re hoping this will have some impact.”

The trial is being conducted at 20 different sites nationally. The first two patients received their transplants at Northwestern Memorial Hospital.

Wounds that don’t heal, the breakdown of tissue, and gangrene can be the result of severely blocked arteries in the leg and sharply diminished blood flow. More than 100,000 limbs are amputated in the United States due to the painful condition call critical limb ischemia (CLI).

Affecting 1.4 million people, the emerging health problem is serious. By the time they reach the age of 70, and estimated 15 percent of the population will suffer from this disease.

Patients who have exhausted all other medical options including angioplasty, stents and bypass surgery to repair blocked circulation in their legs were the target of the Northwestern-led phase I/IIa study, which will include 75 people with CLI around the country.

Affecting about 10 million people in the United States, critical limb ischemia is the result of advanced peripheral artery disease. In peripheral artery disease, people develop blockages in their arteries and vessels that slow or stop the blood flow to their legs.

The condition is called CLI when they have wounds on their legs or feet that will not heal and pain at rest in their lower legs. If left untreated, CLI can result in a patient having toes, a foot or even a leg amputated.

People begin to experience pain when they walk, then when just sitting, as CLI progresses. Since blood flow decreases when people lie down, the pain is the worst at night. In order to lessen the pain and aid in blood flow, some even sleep in chairs.

“Peripheral artery disease is a big health problem,” Losordo said. “There is an emerging awareness of this disease on public health.”

The risk of developing the condition is elevated by high blood pressure, diabetes, high cholesterol and smoking.

However, Losordo points out that, “some people don’t smoke, have diabetes or high blood pressure and can still have blocked arteries in their legs.”
Losordo uses the subject’s own purified stem cells for the randomized, double blind, placebo-controlled trial. CD34+ stem cell from bone marrow are first released into the blood stream by a stem cell stimulating drug. The patient takes this drug for five days prior to the stem cell extraction. Then, the CD34+ enriched blood is obtained by way of an intravenous line that is inserted into a subject’s vein to collect blood through a machine that removes a population of blood cells. Losordo further selects and enriches the cells to select only CD34+ cells.

In order to treat heart disease, induced pluripotent stem cells or iPS cells will be used in a joint study by two professors from Osaka and Kyoto university.

The joint research will be conducted by Osaka University Professor Yoshiki Sawa, who has treated heart disease using cell sheets created from muscle, and Kyoto University Professor Shinya Yamanaka, who created iPS cells that can develop into various types of cells, such as organ or tissue cells, from ordinary human skin.

Cardiac muscle regeneration treatment is the focus of their research.

Yamanaka will be the leader of a newly established iPS cell research center at Kyoto University. The announcement was made on Tuesday.

Using human thigh muscle, Sawa and his research team created cell sheets last year. The heart function of a patient who was a heart transplant candidate was improved when the cell sheets were attached to an area around the heart.

Sawa hopes to turn iPS cells into cardiac muscle cells since the cell sheets do not change into cardiac muscle. He hopes to apply the new research findings to the treatment.

Sawa said, “I’d like to create new cell sheets from new materials using iPS cells, make the sheets available in many cases and enhance the sheets’ practicality.”

The planned research center will be part of the Institute for Integrated Cell-Material Sciences, a world-class research institution that opened in October in Kyoto University.

Several institutions including Kyoto’s University’s Institute for Frontier Medical Sciences will help staff the center with several part-time teams of researchers. The center will also be comprised of a full-time team of 10 to 20 professors, associate professors, researchers and engineers.

The researchers are aiming to develop a safer method of creating iPS cells while sharing their research results. Studying technologies to turn iPS cells into cells for particular purposes is also on the agenda.

Yamanaka said at a press conference on Tuesday that he hoped the planned center would be a research facility open to researchers around the world covering basic to clinical medicine.

“I’d like to nurture young researchers because iPS research requires 10 to 20 years of effort,” he said.

A private incubation facility in Shimogyo Ward, Kyoto, will temporarily host the center in a research lab at the Kyoto Research Park.

With the intent of guiding Japan back to leadership in the field of biotechnology, the Koizumi government adopted a new strategy six years ago.

This did not mark the first time that a national policy initiative of this type was put into effect. And as the current administration tries to capitalize on an exciting stem cell breakthrough, Japan is on the verge of another.

Leading countries have surpassed Japan since 2002.

Japanese biotech drug development, as a ratio of overall drug development, lagged the US, Britain, France and Germany by about 50 per cent according to a report published last year by The Office of Pharmaceutical Industry Research.

Though it is generalization that doesn’t sit convincingly with the nation’s international scientific patents, or Nobel Prize winners over the past 20 years, the disappointing performance in applied biotechnology is often attributed to Japanese science’s alleged weakness at radical innovation.

However, it goes some way towards explaining the surge of official optimism that has built up behind Shinya Yamanaka’s induced pluripotent stem (iPS) cell research team at Kyoto University’s Institute of Frontier Medicine.

It remains to be demonstrated, however, that ministers and officials understand their contribution to previous shortcomings: ponderous and intrusive forms of regulation and administrative guidance that hobble Japanese scientists in the rapidly moving areas of medical and biological R&D.

In the late 1980’s, because of the countries excellence in science education, a high level of government commitment, and track record of converting research into commercial and clinical innovation, Japan was widely expected to become the dominant nation in the exciting new field of biotechnology even at senior policy levels in the US.

Intense bureaucratic supervision usually accompanies a high level of official commitment to an undertaking in Japan, and this is one reason why the biotechnology revolution did not take off in Japan as predicted.

Stem cell research programs can wait 12 months for government approvals, and once under way, pharmaceutical and biotech companies complain, grant-funded research is inflexibly administered.

Approval procedures are far lengthier than in the US and most other Western countries for new drugs and clinical procedures.

However, a fantastic door to opportunity for Japanese leadership has been opened by iPS cell research.

The Yamanaka team’s work seems to have signposted the path to the summit of biotechnology: stem cell therapy with its enormous promise to treat conditions such as Parkinson’s, diabetes, heart and spinal cord damage – but unencumbered by the ethical difficulty of using cloned human embryos or eggs to create embryonic stem cells.

The use of four genetic “transcription factors” to successfully reprogram mice skin cells into becoming stem cells was announced by Yamanaka in June. Another team from the University of Wisconsin was able to produce human iPS cells in November. Not long after, Yamanaka’s group succeeded in making iPS cells using only three transcription factors.

Since the gene c-myc can often cause tumors, they omitted it from the other four.

National admiration has risen for Yamanaka and the world’s attention as focused on the rush of innovation.

But almost invariably, a glum recitation of previous shortfalls in Japanese biotech comes out of what begins as news of further advances in the science or more government support for developing the technology.

The reason is not difficult to see.

Japan imposes the heaviest regulatory conditions of any country that permits embryonic stem cell research. So it is not difficult to at least partially understand why Yamanaka moved into iPS research.

He has complained about the Government’s “terrible regulations and crazy policies that crush any long-term projects”.

Other aspects of the iPS discovery have reached another breakthrough point said Yamanaka in an interview with Tokyo reports last week. However, stem cell therapy is still years away from clinical application he said.

“The other applications, like toxicology and drug development, it’s ready to go,” he said.

“We can use iPS cells in these applications today, if somebody can pay a lot of money – like pharmaceutical companies.”

Those applications involve using iPS cells to create, for instance, neural cells outside someone’s body so they can be tested for personal disease factors, or for an exactly tailored drug treatment.

An immediate start to