It sounds like a far-fetched plot-line on your favorite TV hospital drama, but a team of doctors at Allegheny Health Network (AHN) will tell you their work is real — and making a difference for some very sick patients.
It all starts with a patient suffering from chronic pancreatitis, which causes inflammation in the pancreas that interferes with digestion and can eliminate the cell clusters that produce insulin (called islets or islet cells), leading to diabetes.
“The disease progresses so quickly and so aggressively that the pancreas starts to digest itself,” says Dr. Rita Bottino, a principal investigator at the AHN Institute of Cellular Therapies. “It can be very dramatic and cause so much pain; the patients have to take very strong pain killers all the time. They cannot go to school or work and may need to go to the emergency room 20 times a year just to treat the pain.”
When other, less drastic treatment options have been exhausted, the patient may need to have their pancreas removed.
“When they remove it, they give the patient pills so he or she can digest food,” says Dr. Massimo Trucco, director of the AHN Institute of Cellular Therapies. “They also remove the other 5 percent of the pancreas, which is the part producing insulin. Generally, they throw away the pancreas.”
If the pancreas is removed, the patient can’t produce insulin and develops diabetes. But discarding the pancreas right away is no longer the inevitable next step.
Now, with the new islet cell isolation laboratory at Allegheny General Hospital (AGH) in Pittsburgh, Dr. Trucco and his team can step in to extract the insulin-producing cells from the diseased pancreas so they can be transplanted back into the patient’s body.
The process begins about 135 miles northwest of AGH in an operating room at the Cleveland Clinic. Surgeons remove the patient’s diseased pancreas, put it on ice, and get on the road to Pittsburgh. The organ reaches the AGH islet cell isolation laboratory around 2:30 p.m.
“The organ is usually a little damaged because of the surgery and the auto-digestion,” Dr. Trucco explains. “Fortunately, there is a very thin membrane — kind of like a balloon — around the islet cells, so the idea is to digest the tissue in a way that the islet cells are separate from the rest. Not too much, because you don’t want to destroy the islets, but enough that you separate the rest of the pancreas from the islets.”
Dr. Bottino has been studying islet cell isolation for more than a decade and credits her team’s experience for the program’s high success rates.
“It’s important to say it’s experience and not a technique, because every organ is different, especially with chronic pancreatitis,” she says. “Every time we receive an organ, it has a special, unique condition. So we use our experience to apply different technical approaches to try to get as many islet cells as possible. So it’s a little bit more of an art than a technology. The frame is technological, but some decisions have to be made based on experience.”
Once the islet cells are isolated (between 200,000 and 300,000 per donor), they’re placed in an IV bag and then it’s time to get back on the road. Two cars — each carrying a doctor from the team — make the return trip to Cleveland, just in case one of them is waylaid by a flat tire or other mishap. The doctors arrive just before midnight to transfuse the islets back into the patient who’s suffered from pancreatitis.
“Once the patient doesn’t have a pancreas anymore, he or she is essentially diabetic until the transfusion of the islets is complete and successful,” says Dr. Trucco. “We put the islets into the portal vein, which is the vein that supplies blood to the liver. When these ‘balloons’ of cells get to the capillaries of the organ, they get stuck because the capillaries are too small, and so the balloons park in the liver. The cells stay there and they do their job. We go very slowly in transfusing the islets to avoid an excessive increase of blood pressure into the liver.”
“Studies have proven that islet transplantation when a total pancreatectomy (removal of the pancreas) is required can, with a relatively low risk, help a patient not become diabetic at all,” Dr. Bottino adds. “Some of these patients produce enough of their own insulin for many years. But even those who do not make enough insulin, they have better management of their diabetes than those who do not have the islet transplant.”
Dr. Trucco laughs warmly when people suggest this sounds like science fiction. “It’s not science fiction, it’s mechanical work more than anything,” he says. “It’s a delicate mechanical procedure.”
After the islet cells have been relocated to the liver, patients can start the recovery process. Most children recover well; 35 percent of them don’t need to take insulin after the procedure, for example. The process can be more complicated in adults, though, because many cases of pancreatitis are caused by alcoholism and while breaking the addiction can be challenging, it’s essential for a full recovery.
“But they’re happy because they’re no longer in pain,” Dr. Trucco says, “they can live their lives again, and needing [only] a little bit of insulin is better than nothing.”
The AHN team is also interested in how long the transplanted islet cells are effective. The process has only been an option for a few years, so there’s no way to know exactly how long the transplanted cells will keep working.
“The islet cells in the liver are not in their normal physiological place, so it may be that the effect will not last 40 years,“ says Dr. Trucco. “But any time we can give these patients is a benefit.”
For the moment, only a few hospitals across the country are performing these islet cell transplants because the number of eligible patients is relatively low. Worldwide, Dr. Bottino estimates a few thousand islet cell transplants have been performed to date. The AHN team is interested in offering the procedure locally if patient demand increases.
The Institute of Cellular Therapeutics also supplies research donor islets to Mt. Sinai Hospital in New York City and the medical centers at Stanford and Vanderbilt universities, and the universities of Pennsylvania, Miami and San Francisco, among others.
“The islets we isolate here are sent to different laboratories, and each one specializes in something different, like the immune system or physiological differences or genetics,” says Dr. Bottino. “It optimizes the work because every facility is maximizing its expertise.”
The day I visited the Institute, they were preparing to receive a pancreas from a deceased donor who had type 2 diabetes — making the organ ineligible to be used in a transplant but still helpful to medical research. The team isolated the islets, packaged them up and sent them out to five laboratories studying these cells.
The AHN Institute is the only laboratory in the U.S. that reliably isolates islet cells from people with type 1 diabetes. It’s a feat no one bothered to try for a long time because — by definition — the immune system destroys the islets (and the beta cells inside them) of people with type 1 diabetes.
“We have an opportunity as a laboratory to collaborate with universities across the United States, and they are interested in studying the residual beta cells from type 1 diabetics,” Dr. Bottino explains. “Of course, they don’t expect us to find a lot of the cells, but they asked us to work with them. To our surprise, and maybe it shouldn’t be a surprise, yes — it is possible to isolate some of the beta cells that are still in the body. So some of the researchers we’ve been working with are now developing a better understanding of what happens in the beta cells, the pancreas and the islet cells during the development of type 1 diabetes.”
The team at the Institute has isolated islets from both patients recently diagnosed with diabetes (in the past two years) and diagnosed as long as 30 years ago. In each case they were able to find islets to study, and the islets are showing researchers how type 1 diabetes evolves over time.
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