Harvard researchers have pioneered a technique to grow by the billions the insulin- producing cells diabetics lack, a breakthrough that may create new ways to treat the disease.
The breakthrough comes after 15 years of seeking a bulk recipe for making beta cells, which sense the level of sugar in the blood and keep it in a healthy range by making precise amounts of insulin, according to Harvard scientists led by Douglas Melton, who published their work Thursday in the journal Cell. The process begins with human stem cells, which have the ability to become any type of tissue or organ.
The technique is an important step toward understanding and treating diabetes, a condition in which the pancreas's beta cells are insufficient or dead. Diabetes affects 347 million people worldwide, and its chronic high blood sugar levels can injure hearts, eyes, kidneys, the nervous system and other tissues.
"This is part of the holy grail of regenerative medicine or tissue engineering, trying to make an unlimited source of cells or tissues or organs that you can use in a patient to correct a disease," said Albert Hwa, director of discovery science at JDRF, a New York-based diabetes advocacy group that funded Melton's work.
The procedure for making mature, insulin-secreting beta cells has taken years of painstaking research that led to a 30- day, six-step recipe, Melton said. Laboratories will be able to use the cells to test drugs and learn more about how diabetes occurs, he said.
"They had to go through an awful lot of trial and error to get to this," said Jeanne Loring, director of the Scripps Research Institutes's Center for Regenerative Medicine in La Jolla, California. "The proof will be in how well this protocol works for people in other laboratories."
People with type 2 diabetes, in which the body loses its ability to produce insulin over time, usually take drugs that boost its production. About 15 percent of patients with type 2 can't make enough of the hormone, even with drug treatment, and must take daily injections to replace it, Melton said.
Type 1 diabetes destroys beta cells, and patients must carefully monitor their food and exercise while injecting appropriate doses of insulin to keep blood sugar levels in a healthy range. While self-treatment technology has improved, nothing may replace human beta cells for controlling blood sugar, Melton said.
"They squirt out, or secrete, just the right amount of insulin," he said in a telephone call with reporters. "It's so exquisitely accurate that I don't think it will ever be reproduced."
Transplants of beta cells from deceased donors into diabetes patients are relatively rare, with only about 1,000 performed to date, Hwa said. The cells are difficult to get, and the drugs needed to protect foreign beta cells from the patient's immune system carry risks, he said.
With ample supplies of beta cells, scientists will be able to focus on the best approaches to transplantation, Melton said. His and other labs are focusing on ways to "encapsulate" the cells in materials that deter immune system detection without the use of drugs, he said.
"We're thinking about it as sort of a tea bag," he said. "It would allow the cells to read out the amount of sugar in the blood and squirt out the right amount of insulin."
ViaCyte, a closely held San Diego-based company developing treatment for diabetes, said on Oct. 7 that it will begin testing an implanted cell therapy called VC-01 in patients. The company's technique involves implantation of partially mature stem cells that become islets, structures that contain beta cells, said Paul Laikind, ViaCyte's chief executive officer.
ViaCyte has developed a device, called Encaptra, that keeps the islets safe from immune cells, Laikind said. If safety trials in three patients are successful, the company will begin testing larger doses of the cells in 36 patients next year.
Johnson & Johnson, which is also developing cell-based therapies for diabetes through its Betalogics unit, has invested in ViaCyte. J&J paid $20 million in August for the right to evaluate a deal related ViaCyte's product at a later date, Laikind said.
Drugmakers including Novo Nordisk, Sanofi and Eli Lilly & Co. last year sold $55 billion worldwide in diabetes drugs, the third-biggest-selling class after cancer treatments and pain therapies, according to IMS Health Holdings Inc. Islet cell replacement promises to threaten some of those companies' sales, Melton said.
"Do they wait until this is a disruptive technology that affects their markets, or do they move forward early?" he said. "We all want this to be commercialized so it's available to all patients. We're not interested in just treating a handful of people."
Melton formerly focused his studies on how organisms grow and develop, until his two children were diagnosed with type 1 diabetes. His early efforts grow to beta cells were hindered by restrictions former President George W. Bush put on human embryonic stem cell research in 2001.
Citing concerns about the destruction of human life, Bush said federal money could be used for research on only a few dozen existing embryonic stem cell lines. With funding from JDRF and other sources, Melton pushed for the creation of more stem cell lines from embryos that weren't suitable for human reproduction, and distributed these to other labs. The restrictions were overturned in 2009.
"This would not have been possible without philanthropy," Melton said. "Remember the years that the government thought that this work shouldn't be done?"