Don’t look for this just yet at your neighborhood clinic, but Minnesota scientists are pushing stem cell therapies into new frontiers — into territory that is so open that doctors and regulators still are shaping practices and policies as they go along.
In one breakthrough, researchers at Mayo Clinic in Rochester obtained stem cells derived from the bone marrow of heart disease patients and guided the cells to help heal, repair and regenerate damaged heart tissue. This is “landmark work,” said an editorial accompanying their research report in Monday’s Journal of the American College of Cardiology.
And last week, University of Minnesota researchers reported in the New England Journal of Medicine that they had for the first time used stem cells from bone marrow to help children who suffer from a rare, fatal skin disease.
While these advances are significant, they also show why we have to be patient about waiting for stem cells to deliver their seemingly magical healing power for every day therapy. That has been especially true while ethical, religious and political concerns held up research on stem cells derived from early embryos.
But even with so-called adult stem cells (those not from early embryos), it takes years of painstaking work to isolate just the right cells and then concoct cultures that will not only nurture them in the laboratory but also coax them to perform new functions.
Some clinics already have treated patients with adult stem cells taken from their own bone marrow or the synovial fluid that nurtures and lubricates joints.
Colorado-based Regenerative Sciences Inc. is battling the U.S. Food and Drug Administration in court over its Regenexx procedure. The therapy involves isolating stem cells from the bone marrow of a patient with a joint injury, growing more of the cells in a culture that includes growth factors from the patient’s blood and then placing the cells in the injury area to facilitate healing.
The FDA asserts that the prepared cells are a drug that should be regulated. Regenerative Sciences argues in court documents that it is not injecting foreign drugs into patients but instead facilitating the body’s natural healing processes. The agency went to federal court in the District of Columbia this month, seeking an injunction to halt any use of the procedure until the dispute is settled. Watch for more coverage of this landmark dispute in this blog.
Meanwhile, the Minnesota research shows that we shouldn’t expect overnight breakthroughs from stem cell studies. Instead, we must wait for results that come from years — even decades — of slow, arduous work.
The Mayo research is a prime illustration. It was done at Mayo and two cardiovascular centers in Belgium.
Researchers obtained bone marrow stem cells from 11 patients undergoing coronary bypass surgery. Extensive molecular testing of the cells revealed that those from just two individuals had the right stuff to potentially regenerate bodily tissue.
The daunting challenge was to steer those cells toward the specific mission of repairing damaged heart tissue. The cells had to be nurtured and reprogrammed in a “cardiogenic cocktail.”
This is tricky work that has taken decades of trial and error by scientists around the world. Identifying the molecular signatures of the best regenerative cells was a big part of it. Another critical part was developing just the right recipes for “cocktails,” or laboratory cultures that could steer a set of cell lines toward behaving as if they belonged in the heart rather than in bone marrow.
In the Mayo research, mice with heart failure were injected with the “guided” cells. After a year, they demonstrated significant heart function recovery and they survived longer than other mice treated with unguided stem cells or saline.
“Specifically, researchers found that the heart tissue healed more effectively; that human cardiac and vascular cells were found participating in the regeneration, repair and strengthening of heart structures within the area of injury; and that scars and vestiges of heart damage appeared to fade away,” said a Mayo statement summarizing the findings.
Success in mice is not the same as success in humans, of course. The next steps, being conducted in Europe, are testing the safety and effectiveness of the cells in humans.
Still, Mayo seems to anticipate a not-too-far-off day when therapies based on such cells actually could heal damaged hearts. It has licensed the technology to a Belgium-based company, Cardio3 Biosciences, in exchange for equity in the venture.
The U of M discovery involved coaxing stem cells from bone marrow into repairing skin in children with a rare and extremely painful disease. Veteran medical school researchers — Dr. John E. Wagner and Dr. Jakub Tolar — collaborated with colleagues in Portland, Oregon, the United Kingdom, and Japan.
They were building on transplantation work that started at the U of M in the 1960s.
“Whether stem cells from marrow could repair tissues other than itself has been quite controversial,” Wagner said in a statement. “But in 2007 we found a rare subpopulation of marrow stem cells that could repair the skin in laboratory models. This astounding finding compelled us to test these stem cells in humans. This has never been done before.”
Tolar also stressed the high degree of difficulty research teams have had to overcome to get this far: “This discovery is more unique and more remarkable than it may first sound because until now, bone marrow has only been used to replace diseased or damaged marrow — which makes sense.”
Beginning in 2007, the researchers worked with children who suffered with the most aggressive form of Epidermolysis bullosa (EB), a rare, genetic disease that causes skin to blister and scrape off with the slightest friction or trauma. Previously, there was no treatment and no chance for cure. If children with EB did not die of infection in their early life, many developed an aggressive and lethal form of skin cancer as young adults.
Two of seven children in the study died. Wagner and Tolar are measuring progress in the survivors. They have found, Tolar said, that stem cells from bone marrow can travel to sites of injured skin and step up production of something that had been all but missing in these children: collagen 7, a protein that connects and supports skin.
The findings are promising enough to raise hope that EB eventually will come off the incurable list.
But the research isn’t finished.
“We are fully conscious of what we have accomplished so far and the enormity of what else needs to be done,” Tolar said.