Patients with Type 1 diabetes may someday be treated with a single transplantation of pancreatic cells, rather than having to continually monitor their blood sugar levels. A study conducted by an Alpert Medical School student identified a successful way to increase the longevity of these cells in a mouse model.
The findings were published in the journal Transplantation last month.
Researchers co-cultured islets — insulin-producing cells found in the pancreas — with human bone marrow stem cells and injected them into diabetic mice with ineffective immune systems, said John Luo MD ’13, a research associate at Roger Williams Medical Center and lead author of the paper.
Patients with Type 1 diabetes do not produce insulin naturally and therefore cannot regulate their blood sugar without treatment. Islet transplantation is one possible treatment, but the current process is inefficient, Luo said. Mice that received islet transplants using the current technique survived for 40 days on average. But mice who received transplants that included both islets and bone marrow stem cells survived an average of 130 days, according to the paper.
Over three months, blood sugar levels in mice with normal islets remained flat while blood sugar levels of mice with islets grown in bone marrow significantly decreased, Luo said.
Type 1 diabetes patients who struggle with regulating their blood sugar levels with insulin injection have received islet transplantations for 20 years, Luo said. But a single islet transplantation often requires two to three deceased pancreas donors, and patients usually need at least two transplants, he added. The current study shows that bone marrow stem cells increase the longevity of islets in an animal model.
Though islets account for only 5 to 10 percent of the mass of the pancreas, “replacing the small population of islets is difficult to sustain both in vivo and in vitro,” Luo said. The two-year survival rate for islets in humans is 30 percent.
Immune rejection or a lack of supportive environment might explain the challenge of sustaining islets, he said. The study focused on creating a supportive environment for islets with human bone marrow, but Luo called the immune system a “huge concern.” Using immunodeficient mice in the experiment prevented a negative immune response to the islets.
In 2007, Luo and his collaborators published a paper detailing how bone marrow stem cells kept human islets alive for six months in cell cultures — the amount of time required for an approach to be considered effective, Luo said. The 2007 study prompted the team to continue their research and the lab at Roger Williams to designate the research a “flagship” project, he said.
“The next step is to look at the mechanisms. How do you explain the cell mechanisms, and what are the pathways involved?” Luo asked, adding that bone marrow stem cells may stimulate islet growth or prevent islet death.
The basis of these experiments “stems from a lot of serendipity,” Luo said. “We had access to human bone marrow, and we had access to islets.”
Luo said clinical trials for patients who are candidates for islet transplantation could occur within two years. “The ultimate goal is to get rid of insulin injections, which could be dangerous,” Luo said.
James Shapiro, director of the islet transplant program at the University of Alberta, said he is optimistic that “co-transplantation” will be transferred from the lab to a clinical setting. Shapiro helped develop the standard method for islet transplantation known as the “Edmonton Protocol.” Last year, he and his team performed 66 islet transplantations.
Shapiro confirmed the difficulty of islet sustainability — 80 to 90 percent of his patients require multiple transplants, he said.
Transplants keep most of Shapiro’s patients off insulin for three to five years, and when they begin using insulin post-transplant, they are better able to control their blood sugar, he said. “Being able to improve the quality of the (islets) and being able to transform the cells into insulin-producing cells is a major advance,” Shapiro said.