IT HAS been an uplifting week for stem cell research. Not only is US president-elect Barack Obama poised to sweep away restrictions on stem cells when he takes office on 20 January, but a new treatment based on the drug Mozobil promises to harness an individual’s stem cells to help them heal their own bodies.
A few days ago Sara Rankin and her colleagues at Imperial College London announced that Mozobil, in combination with natural growth factors, can free up specific types of stem cells from the bone marrows of mice and send them flooding into the bloodstream.
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The discovery is important because it opens up the possibility of treatments tailored to the individual, who would for example take drugs to stimulate the growth and release of specific stem cells to repair cardiac tissue after a heart attack. Such treatments would be free of the ethical baggage associated with therapies based on extracting stem cells from human embryos – though their development would not remove the need for embryonic stem cell research as they do not cover all cell types.
Treatments to stimulate the bone marrow to make stem cells are already widely used to treat leukaemias and other blood cancers. Based on a natural growth factor called granulocyte colony stimulating factor (GCSF), they prompt the bone marrow to produce extra haematopoietic stem cells (HSCs), which grow into all types of blood cell. These cells can be extracted over weeks and stored ready for transplant into the bone marrow following chemotherapy to kill cancerous blood cells, where they restock the blood cells destroyed by the anti-cancer drugs.
Now Rankin’s team has shown that it is possible to persuade the bone marrows of mice to produce two additional categories of stem cell – mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) – broadening considerably the types of damage and disease that might be treatable. “It’s promoting self-healing,” says Rankin, whose team’s research was published last week in Cell Stem Cell (). “We’re simply boosting what’s going on naturally, and we’ve shown that we can selectively mobilise different types of stem cell.”
“We’re simply boosting what’s going on naturally, and we can selectively mobilise different types of stem cell”
MSCs grow into muscle and bone, and so have the potential to repair cardiac tissue following heart attacks, or to accelerate healing of broken bones or ligaments. They also damp down inflammation, and so could be used to treat autoimmune diseases. EPCs repair blood vessels and form new ones, so they have the potential to restore vital blood supplies to tissues damaged by strokes or heart attacks.
Rankin and her colleagues showed that they could persuade mouse bone marrow to release floods of both types of cell at the same time by giving the mice Mozobil plus a natural substance called vascular endothelial growth factor (VEGF). Rankin’s team also used GSCF and Mozobil in mice to show that, in principle, drug therapies can be tweaked to produce either blood stem cells or those that become muscle, bone and blood vessels.
What is more, the stage is set for these treatments to be tried in people, as both growth factors are available commercially. Mozobil’s maker, of Cambridge, Massachusetts, received approval in December from the US Food and Drug Administration to sell the drug in combination with GCSF for treating lymphoma.
Genzyme told 91av that it is looking into other ways of using Mozobil. “Its novel mechanism of action opens the door for a rich area of research,” says Richard Peters, vice-president of global medical affairs at Genzyme Transplant and Oncology.
One big question is whether the new approach will supplant or simplify other stem cell treatments in development. Many of these rely on extraction and multiplication of specific stem cells from patients’ blood, a process which takes weeks and is technically difficult. Given Mozobil plus growth factors, patients could potentially make extra copies of the same cells in their own bodies.
An run by the US National Institutes of Health included 720 new or ongoing trials which specified enriching patients’ own stem cells outside the body as part of the treatment. In many cases the new drug regime could potentially be used instead.
“Ours is a much more direct approach, and doesn’t have the ethical and regulatory issues associated with other types of stem cell therapy, and it would be a lot cheaper,” says Rankin. But she stresses that the approach can’t be used for every type of disease, and so should not be used by governments as a reason to reduce funding for other stem cell research. She points out, for example, that there are no known bone marrow stem cells that make nerve or brain cells. These can only be made from embryonic stem cells, or from induced pluripotent stem cells produced by introducing genes that coax skin and other cells back into an embryonic-like state.
Robin Lovell-Badge of the UK’s National Institute for Medical Research in London agrees. “It doesn’t change the need to do embryonic stem cell research at all.” Bone marrow stem cells, for example, can’t make insulin-producing islet cells for treating diabetes, he adds.
What Rankin hasn’t shown yet, as she herself admits, is whether the stem cells produced in her study do indeed accelerate or improve healing. And as Lovell-Badge points out, “Giving patients Mozobil plus VEGF could have other effects on the body.”
Tantalisingly, however, there is unpublished evidence that Mozobil-derived EPCs help heal cardiac tissue in mice after heart attacks. The research, presented in 2003 at the American Heart Association’s annual meeting, was led by Atsuchi Iwakura and his colleagues at AnorMed, the company in Boston which originally developed Mozobil. The results show that the hearts of treated mice recovered faster and had less scarring a month after the heart attack.
Rankin favours further research in animals before moving into people, but she acknowledges that all the ingredients are available commercially, and so could be used by anyone contemplating clinical trials. “It’s feasible this will happen in the next five to 10 years,” she says
Stem cell deliverance is nigh
After Barack Obama is inaugurated as US president on 20 January, expect him to make good on his promise back in August to reverse George W. Bush’s restrictions on stem cell research. “As president, on federal funding of research on embryonic stem cell lines created after 9 August 2001 through executive order,” he said.
Now the smart money is on him issuing an executive order himself within days to get rid of the veto that Bush introduced to satisfy opponents of research on human embryos.
Congress may later pass legislation to block reintroduction of the restrictions by future administrations. In a memo to the transition team this week, the in Oakland, California, called on Obama to work with Congress to introduce comprehensive laws overseeing all stem cell research in the US, which at present is completely unregulated in the private sector.
