By Jennifer Nachbur Article published October 18, 2006
Stem cells are full of therapeutic promise. Armed with the almost limitless capacity to copy themselves and grow into many types of cells in the body, they function as the body’s cellular repair shop. While embryonic stem cells have been the focus of heated nationwide debate, many scientists have been quietly examining the potential therapeutic possibilities of two controversy-free and very promising alternatives — adult bone marrow-derived stem cells and umbilical cord blood stem cells.
Adult stem cells, whose main function is to maintain and repair tissue, have been studied since the 1960s. Bone marrow-derived adult stem cell transplants have been used for over 30 years, and umbilical cord blood stem cell transplants have been used for more than 20 years to treat patients with blood cancers. Recent discoveries have shown that these stem cells also have the potential to repair damaged tissue cells in several organs, generating new hope and excitement for researchers seeking better treatment options for a host of illnesses.
For the past several years, a small group of researchers in the Pulmonary and Critical Care Division of the Department of Medicine at the University of Vermont have been gaining international recognition for their work in the area of adult stem cells’ potential role in treating lung diseases. Dr. Benjamin Suratt, assistant professor of medicine, and his colleagues were the first to find evidence that adult human stem cell transplantation resulted in spontaneous cell regeneration in damaged lung tissue and published their findings in the August 2003 American Journal of Respiratory and Critical Care Medicine.
“A number of papers show that adult bone marrow-derived stem cells can be induced to turn into heart, liver or brain or more importantly for us, the lung,” says Daniel Weiss, associate professor of medicine. In the lab, Weiss and his team have successfully isolated adult stem cells from the bone marrow of adult mice and begun to turn them into lung cells, which could result in the development of therapies for emphysema, asthma and cystic fibrosis (CF).
Weiss’ current adult stem cell research, an outgrowth of his past cystic fibrosis gene therapy work, shows promise when the two therapies are combined. His theory maintains that stem cells isolated from the bone marrow could be manipulated to express the normal CF protein using a gene transfer technique. Then, explains Weiss, the corrected stem cells could be administered back into the CF patient and coaxed to go to the lung.
“What we’re doing is taking these two sophisticated, high-tech techniques and combining them in a rational way for a disease that’s the result of a genetic defect,” says Weiss, whose research in this area made the cover of the January American Journal of Respiratory and Critical Care Medicine.
Building blocks
Though adult stem cells are able to turn into a variety of cells and tissues, they are not as versatile as embryonic stem cells. A viable and legal alternative is umbilical cord blood stem cells. Through a program run in collaboration with Dr. Ira Bernstein, professor of obstetrics and gynecology and director of maternal fetal medicine, and the labor and delivery suite at Fletcher Allen Health Care, Weiss and colleagues have had the opportunity to investigate the therapeutic capabilities of cord blood stem cells. To date, the team has been able to induce the cord blood stem cells to begin to turn into lung cells in Petri dishes and has started transplanting these cells into immunotolerant mice.
On the horizon for Weiss is a newly-approved protocol with the Cystic Fibrosis Foundation that will allow him and his colleagues to take this research one step further by collecting cord blood from babies who have CF. The goal will be to isolate the cord blood stem cells and use gene transfer/therapy techniques to correct the CF defect. Weiss, who receives funding from the National Institutes of Health, the CF Foundation, American Lung Association and the Tulane Primate Research Center, says his group is also pursuing this approach for emphysema by using stem cells to grow new lung tissue.
Focusing less on regeneration and more on repair, Suratt specializes in acute lung injury (ALI) and its most severe form, adult respiratory distress syndrome (ARDS), which may develop after infection, shock and trauma. For the past two years, his work has centered on examining the molecular activity involved in the development and repair of acute lung injury.
Suratt received a $1.9 million, five-year research project grant award in May of 2006 from the National Heart Lung and Blood Institute to look specifically at several cytokines — proteins that function as intracellular communicators and are involved in immune response — and their role in both the development of acute lung injury and recruitment of inflammatory cells and reparative cells. Suratt says there’s an apparent ‘overlap’ period toward the end of the most acute phase of ARDS, where the tail end of the inflammatory response is being driven by the same cytokine environment that is also suspected to be recruiting stem cells to repair the injury.
One particular cytokine that appears to carry this responsibility — Stromal Derived Factor 1 (SDF1) — plays a role in both stem cell trafficking as well as metastasis of cancer cells. “It’s also widely believed that SDF1 is responsible for the trafficking of a number of different cell types to the lung. The new grant is directed specifically at examining the role of these cytokines … in the inflammatory cell trafficking that overlaps with the stem cell trafficking” Suratt says.
The group, which includes Jeffrey Spees, assistant professor of medicine, has been working to create a stem cell center at UVM. Spees’ role is to direct the new Stem Cell Core facility, provide expertise in stem cell biology and isolate, culture, characterize and provide the stem cells that the group uses in their research. Spees is already providing isolated cells to a number of College of Medicine investigators, as well as national and international researchers.
While at Tulane’s Center for Gene Therapy, Spees and colleagues were the first to show that human stem cells could fuse with lung epithelial cells during the repair process. Spees has continued to work on cell fusion and is also examining the effects of factors secreted by bone marrow stem cells on the growth and support of native adult cardiac stem cells with the goal of finding out whether or not they will initiate repair in the heart. With Dr. David Schneider, associate professor of medicine and director of cardiology, and Dr. Burton Sobel, professor of medicine, he uses a mouse model of heart attack, which partially blocks the blood supply to the left ventricle of the heart. In their experiments, which focus on injecting adult bone marrow cells intravenously into immunodeficient mice, they have observed improved heart function in the treated mice.
“We don’t actually know what the most important effects or mechanisms are,” says Spees, “but you generally have improved heart function and reduced fibrosis.”
The group’s collective hope is to recruit additional stem cell researchers and to continue to broaden the scope of their research in the near future. With their current research efforts, available funding and proven track record in pushing forward, this new venture is becoming a reality. Stem cell researchers, like the cells themselves, are well situated to grow into new structures.
