Injecting a patients' own stem cells into their leg muscles could create new blood vessels, eliminating pain from bad circulation and helping to prevent gangrene or amputations, new research indicates.
The study, described this week in The Lancet medical journal, is the first demonstration that implanting stem cells into humans can result in new blood vessel networks, a process called angiogenesis.
Experts say the findings offer hope to millions of people worldwide who suffer pain in their limbs because of clogged arteries but can't have an operation.
Controlling blood vessel growth is an emerging field of medicine. In the case of cancer, which spreads by sprouting its own blood vessel network, scientists are testing drugs to thwart angiogenesis.
However, when parts of the body are starved of oxygen because blood vessels supplying them are blocked, doctors want to boost blood vessel growth, treatment they call therapeutic angiogenesis.
The main focus of research is on the heart, limbs and, in the future, brain. Heart attacks, limb amputations and strokes can result from severe circulation problems. Another target is sores that fail to heal.
Experiments so far have involved infusing human proteins needed for new blood vessel growth into the veins or injecting muscles with genes that make the proteins.
"This is truly a landmark paper because of its use of stem cells to induce angiogenesis," said Dr. William Li, president and medical director of the Boston-based Angiogenesis Foundation, who was not involved in the research.
"It's a brand new approach to treating limbs starved of blood supply," Li said. "They were able to eliminate rest pain in 80 percent of their patients. That is striking. You don't see that with other treatments."
The study was done by scientists at three Japanese universities: Kansai Medical University in Osaka, Kurume University School of Medicine in Kurume and Jichi Medical School in Tochigi.
It involved 45 people with severe blood circulation problems in their legs. About half had already had a bypass operation in their legs, nearly half had gangrene and 69 percent had diabetes. Many had sores that wouldn't heal, suffered pain in their legs even when sitting and were not candidates for surgery or other artery-widening techniques.
The first part of the experiment involved 25 patients in a pilot study to test how many people would be needed to demonstrate whether the treatment made a difference.
In the pilot study, bone marrow was extracted from the patients and stem cells injected into their worst leg. Saline solution was injected into the other leg.
The main study involved 20 other people in whom both legs were critically starved of blood flow. They had their bone marrow stem cells injected into one leg, randomly chosen, and regular blood injected into the other leg. Before the experiment, everyone had an angiogram, a scan that shows the blood vessel network.
The scientists used several measurements to gauge the success of the treatment.
The legs that got the stem cells had more improvement than the others on a test comparing blood pressure in the ankle with that in the arm before and after treatment. Similar results were seen in a second circulation test that measured differences in oxygen inside and outside tissues.
Pain while sitting down disappeared in the stem cell-injected legs of 16 of the 20 people in the main study, but 17 out of the 20 legs that got the blood injection remained painful. That improvement lasted for the six months of the study.
X-rays before and after the cell implantation showed increased blood vessel networks in 27 of the 45 who got the stem cells in the two studies.
Toe amputations were avoided in 15 out of 20 people, and unhealed wounds improved in six out of the 10 patients who suffered from them.
Ira Herman, a professor of physiology at Tufts University who was not involved in the research, said the most impressive findings came from leg specimens of one patient who got stem cells in one leg and saline in the other but died half way through the trial of an unrelated heart attack. The examination found a striking increase in blood vessel numbers in the leg injected with stem cells.
"It's just remarkable," he said. "You can't help but be impressed by the collection of data."
One question that remains unclear is whether the stem cells actually became blood vessel cells or whether they simply released growth factors that prompted other cells to construct new vessels.
Dr. Frank Sellke, chief of cardiothoracic surgery at Harvard Medical School who was also not involved in the study, said the stem cell approach may have great potential.
"There is evidence that the bone marrow cells will actually seek out the most (starved) territory. They will circulate and go to where they are needed," he said.