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From stem cells to insulin-producing cells
December 2014
by Lori Lesko  |  Email the author
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CAMBRIDGE, Mass.—When Harvard University researcher Dr. Douglas Melton’s infant son Sam was diagnosed with type 1 diabetes, he dedicated his career to finding a cure. That was 23 years ago, but Melton and his research team have recently taken a giant leap forward for an effective diabetes treatment, as reported in the Oct. 9 issue of the journal Cell.
 
Entitled “Generation of functional human pancreatic beta cells in vitro,” the journal article states that scientists are able to produce, for the first time, human insulin-producing beta cells in the kind of massive quantities needed for cell transplantation and pharmaceutical purposes—cells that are reportedly equivalent in most every way to normally functioning beta cells.
 
Type 1 diabetes is a condition that affects an estimated 3 million Americans at a cost of about $15 billion annually, and occurs most often in children who then have to take insulin the rest of their lives.
 
Melton hopes to soon have human transplantation trials and is hopeful to be able to start using the cells within a few years.
 
“We are now just one preclinical step away from the finish line,” Melton stated in the Harvard Gazette. His daughter Emma also has type 1 diabetes.
 
“You never know for sure that something like this is going to work until you’ve tested it numerous ways,” Melton says. “We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately; that was really exciting.”
 
“It was gratifying to know that we could do something that we always thought was possible, but many people felt it wouldn’t work,” he adds. “If we had shown this was not possible, then I would have had to give up on this whole approach. Now I’m really energized.”
 
The stem cell-derived beta cells are presently undergoing trials in animal models, including non-human primates, the Cell article reported.
 
Elaine Fuchs, a professor at Rockefeller University who is not involved in the work, stated of Melton’s work that it is “one of the most important advances to date in the stem cell field, and I join the many people throughout the world in applauding my colleague for this remarkable achievement. For decades, researchers have tried to generate human pancreatic beta cells that could be cultured and passaged long-term under conditions where they produce insulin. Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes.”
 
Dr. Jose Oberholzer, associate professor of surgery, endocrinology and diabetes and associate professor of bioengineering at the University of Illinois at Chicago, said the work described in Cell “will leave a dent in the history of diabetes. Doug Melton has put in a lifetime of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment.”
 
Melton, co-scientific director of the Harvard Stem Cell Institute and the University’s Department of Stem Cell and Regenerative Biology, says that when he told his son and daughter they were “surprisingly calm” and believed “Dad” could do it.
 
Type 1 diabetes is an autoimmune metabolic condition in which the body kills off all the pancreatic beta cells that produce the insulin needed for glucose regulation in the body. Thus the final preclinical step in the development of a treatment involves protecting from immune system attack the approximately 150 million cells that would have to be transplanted into each patient being treated.
 
Melton is collaborating to develop an implantation device to protect the cells with Daniel G. Anderson, a professor of applied biology and associate professor of chemical engineering at the Institute of Medical Engineering and Science and the Koch Institute at the Massachusetts Institute of Technology (MIT).
 
Anderson stated in the Harvard Gazette that the new work by Melton’s lab is “an incredibly important advance for diabetes. There is no question that ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics. In particular, this advance opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy.”
 
Scientists at MIT have thus far protected beta cells implanted in mice from immune attack for many months, and the mice are still producing insulin, Anderson said.
 
Cell transplantation as a treatment for diabetes is still experimental, uses cells from cadavers, requires the use of powerful immunosuppressive drugs and has been available to only a very small number of patients, the Cell article stated.
 
Dr. Richard A. Insel, chief scientific officer of the Juvenile Diabetes Research Foundation (JDRF), stated that the “JDRF is thrilled with this advancement toward large-scale production of mature, functional human beta cells by Melton and his team. This significant accomplishment has the potential to serve as a cell source for islet replacement in people with type 1 diabetes and may provide a resource for discovery of beta cell therapies that promote survival or regeneration of beta cells and development of screening biomarkers to monitor beta cell health and survival to guide therapeutic strategies for all stages of the disease.”
 
Eliot Brenner, program director of the Helmsley Charitable Trust’s type 1 diabetes program, stated, “The ability to create insulin-producing cells not only has significant clinical potential, but it opens an important new path for researchers to understand and develop novel treatments for type 1 diabetes.”
 
While diabetics can keep their glucose metabolism under general control by injecting insulin multiple times a day, that does not provide the kind of exquisite fine-tuning necessary to properly control metabolism, and that lack of control can lead to devastating complications, from blindness to loss of limbs.
 
About 10 percent of the more than 26 million Americans livingwith type 2 diabetes are also dependent upon insulin injections, and would presumably be candidates for beta cell transplants, Melton said.
 
“There have been previous reports of other labs deriving beta cell types from stem cells; no other group has produced mature beta cells as suitable for use in patients,” Melton says. “The biggest hurdle has been to get to glucose-sensing, insulin-secreting beta cells—and that’s what our group has done.”
 
Code: E121409

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