Joslin Doctor Advocates for Better Islet Cell Access for Researchers
Wednesday, December 17, 2014
As cases of diabetes across the world increase, so does research into causes of and treatment for the disease.
Researching the complexities of diabetes requires access to a host of tissues from the human body. Muscle, liver, fat, heart—cells from all of these organs play a part. One organ in particular serves an important role in the onset and progression of diabetes and it happens to be one of the least easily accessible organs in the human body: the pancreas, which houses islets, which in turn hold the insulin-secreting beta cells that falter and fail over the course of diabetes.
But an influx of researchers is stretching the already strained supply of islet cells available. Rohit Kulkarni, M.D., Ph.D., Senior Investigator in the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center and Associate Professor at Harvard Medical School, is working with researchers to lobby the government for more resources and support.
“Obtaining human islets for research in diabetes is an important component that will allow investigators to gain critical insights into how insulin-producing cells work,” said Dr. Kulkarni. “These experiments are of high significance in the overall goal of developing therapeutic approaches to successfully replace and/or regenerate insulin-producing cells in all forms of human diabetes.”
For decades, researchers have been able to get around the difficulties in acquiring human islets by using the same cells from rodent models. But recent research shows that while rodent islets are fair analogs, they differ enough from human islets to cause some problems when trying to translate research done in rodents into human models.
“Research over the last two or three years specifically has focused on many of us trying to replicate what has been done in rodent islets,” said Dr. Kulkarni. His experience is part of a greater trend throughout the scientific community studying beta cells. They need to ensure the discoveries they made using rodents hold true in humans.
The labs using human islets get their supplies from a network of six centers collectively known as the Integrated Islet Distribution Program (IIDP). The IIDP notifies researchers via email blast that islets are available to ship. Researchers claim islets on a first come, first served basis of up to 10,000 islets at a time. This method leaves some labs stagnant, waiting for islets for weeks on end.
In 2010 only 35 labs were working with human islets. Now, in 2014, that count has increased to 104—and growing, due to a new initiative by the National Institutes of Health (NIH) called the Human Islet Research Network, or HIRN. With HIRN, the NIH hopes to fund additional labs undertaking studies involving human islets.
Initially, the IIDP had only secured funding through 2015. To make sure the IIDP can continue to function at its current level for the next two to three years, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) decided the price of individual islets would quadruple as of January 2015—up to $0.12 per islet from the current cost of $0.03. The labs requesting the islets are expected to shoulder the extra $0.09. Considering the large number of islets required for any given experiment, the upcharge will add an unexpected burden on a lab’s budget, while the access to islets remains the same.
“So that is a little bit of a setback for us because I’d like to spend those funds for other work in my lab on the same project, but not put everything onto the human islet,” he said. The NIH and the JDRF have recently announced a Request for Applications that promises to supplement the cost of islets for existing grants. But whether or not this offer of support will continue into the future calls for proposals remains a question.
Dr. Kulkarni, along with Andrew Stewart, M.D., Director of the Diabetes, Obesity and Metabolism Institute at of Mount Sinai Hospital in New York, is leading the call for a number changes to the organization, transparency, and productivity of centers that isolate and distribute islets. They and a number of colleagues discussed the issues and possible solutions at a Keystone meeting in April 2014; the points of discussion were also recently captured in a whitepaper Drs. Kulkarni and Stewart submitted to the NIH.
One solution they presented involved increasing funding for the IIDP to isolate and distribute more islets.
“From our own calculations and also from talking to the IIDP and other colleagues we think that getting about $2 to $2.5 million more per year [to the IIDP] would allow a doubling of these islets. And the question is where is this funding coming from?” said Dr. Kulkarni.
They suggest a number of ways to stretch funding, from partnering with different industries to repurposing the soon-to-close centers dedicated to harvesting islets for transplants. They also recommend the already existing IIDP centers double up in their function by analyzing the phenotypes of the human islets they distribute. Such NIH-funded centers already exist for mouse islets, and researchers need much more information about human islets to make sure their research is consistent, such as gender, BMI and health histories (all relevant data is de-identified to comply with personal health privacy).
Demand aside, other issues keep the availability of islets low. Dr. Kulkarni notes that the number of usable islets from a shipment of 10,000 ranges between 1,000 to several thousand. This inconsistency in the quality of islets upon arrival needs to be addressed by encouraging improved isolation techniques, ensuring uniformity throughout all branches of the IIDP. Some of these improvements are being considered and Dr. Kulkarni and his colleagues hope this effort will continue.
And demand wouldn’t be such a problem if more pancreases were harvested from organ donors. Gathering islets through biopsy isn’t an option, since it leads to pancreatitis. More than 16,000 kidneys and 7,000 livers were harvested in 2012, according to a recent Nature article. Compare that to the approximate 1,900 pancreases removed during the same time period. Removing a pancreas and then isolating islets from that pancreas requires specialty training, which is why many organ procurement agencies leave pancreases behind. Dr. Kulkarni and colleagues recommend more comprehensive training, as one potential approach, to make sure the pancreases of organ donors don’t go to waste.
Dr. Kulkarni and the other signatories on the whitepaper recognize that the NIH shouldn’t shoulder the entire burden, so they recommend researchers come up with creative ways to use fewer islets in experiments, while still achieving usable results. They also suggest that labs contribute ideas for quality standardization procedures to make sure all centers are using the most up-to-date techniques.
With the inevitable crush of new researchers vying for the same number of resources, Dr. Kulkarni foresees his lab’s productivity decreasing.
“There’s 10 people in my lab who want to work with the islets,” he said. “But only one or two can. And so that’s the limitation.”
Help Dr. Kulkarni bring attention to this important issue by writing a letter to your congressperson and senator. “The more visibility we have, the more involved that people get the better it will be,” he said.
Discover some of the ways Dr. Kulkarni uses islet cells in his research
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