Islets for US
PANCREATIC ISLETS ALLOTRANSPLANTATION
BRITTLE TYPE 1 DIABETES MELLITUS
Pancreas and Islet Processing
Pancreas and islet processing take place in a special laboratory- "GMP facility"
This laboratory meets all FDA requirements for cell and tissue processing for clinical applications and follows current Good Manufacture Practice rules and regulations. Standardized and validated islet processing, carried out in the controlled environment of the cGMP facility, allows for the highest quality of final islet product.
Islet Processing Teams in many centers involved in clinical trials are very experienced, having performed over 200 islet isolations. Our success in islet transplantation is strongly related not only to the experience but also the dedication of our team. Since the pancreas needs to be processed as soon as it arrives, our team members are on call 24/7.
Pancreas processing includes enzymatic digestion, islet separation, purification and culture. Prior to the islet release for the transplant, islet cells are counted and tested for confirmation of their quality and sterility.
The information below is for adult patients with type 1 Diabetes Mellitus (T1DM).
Unfortunately, islet transplantation cannot be applied in children with T1DM and patients with type 2 diabetes.
Today, modern insulin therapy remains the best treatment option for the majority of patients with T1DM.
Term "brittle" T1D has been replaced by leaders in endocrinology by "uncontrolled diabetes" or "labile diabetes" in order to stimulate patients and medical providers to analyze the reasons for poor glucose control, and optimize medical treatment for each individual patient instead of giving up and blaming the "brittle" form of disease. And this is an excellent approach.
Unfortunately, there is a small group of patients who suffers from poor glucose control despite the best efforts and optimal medical recommendations by highly experienced diabetic educators and endocrinologist. Poor glucose control leads to debilitating and life-threatening secondary diabetic complications like hypoglycemic unawareness, kidney disease, neuropathy, heart and blood vessels disease, blindness, foot infection leading to amputations,
Pancreas or pancreatic islet transplantation remains then only therapeutic option for this highly selected patients. with T1DM, those who fit one of two categories:
A) T1DM patients whose life is extremely compromised by severe hypoglycemic episodes in the course of hypoglycemic unawareness, despite optimal insulin treatment under the guidance of an experienced endocrinologist (diabetes doctor). Those patients we still call "brittle " type 1 diabetics to distinguish them from those who can still benefit from optimization of medical therapy and should not consider transplant yet.
B) T1DM patients who have already developed kidney failure, and could benefit from simultaneous (at the same time) kidney and pancreas transplantation, allowing the patient to not only stop insulin, but more importantly, improving their quality of life and life expectancy.
A pancreas for transplantation as the whole organ or as islet transplant comes from a deceased donor.
We can not take a pancreas for transplantation from a living donor.
Regardless if a whole pancreas or only islets are transplanted, a patient will need to take medications to prevent rejection of the transplant (the body attacking the new organ or islets). Those medications are called immunosuppression or anti-rejection pills. . These will need to be taken for the life of the transplant, as long as the organ is working. If these medications are not taken, the transplanted organ will become damaged and lost.
The anti-rejection medications are vital to protecting the transplanted organ, but they can have a variety of side effects, including, but not limited to:
Increased risk of infection
Stomach pains, diarrhea, constipation, nausea or vomiting
Headache, tremors, dizziness
High blood pressure
Decreased cell counts (anemia, neutropenia)
Long term risk of certain cancers including leukemia and skin cancer
Many side effects can be managed by adjusting medication doses and checking medication levels to make sure they are not too high (putting patients at risk for infection) or too low (putting patients at risk for rejection).
Because of this, we ask patients to come to clinic frequently (initially 2-3 times a week) to communicate with their care team, along with adjusting and optimizing their dose of anti-rejection medications. Once the dose of the medications is optimal, patients will need to get blood work done once a month and eventually less often.
The pancreas transplantation procedure is a major operation where patients are put to sleep (under general anesthesia). It involves connecting the pancreas to a blood supply (vascular anastomosis) and your intestines (bowel anastomosis). Despite the best surgical technique and experience, there is still a 10% chance of losing a pancreas graft within the first 2 weeks after the transplant and a 10% chance for re-operation due to bleeding or infection.
Pancreatic Islet Isolation and Transplantation
Pancreatic islet allo transplantation has been developed as a minimal invasive procedure as an alternative to a whole pancreas transplant to avoid major surgery and the related complications.
However, since islet cells are isolated from a deceased donor pancreas, the patient still requires the same immunosuppression and similar management as after the whole pancreas transplantation described above.
A pancreas comes from a deceased donor, just as a whole organ pancreas does,however, we select the donor pancreas based on special islet related criteria that was developing through a multi-center collaboration (see publication).
The pancreas then goes to be processed before transplantation. Pancreatic islets are isolated by Dr. Witkowski’s team at The University of Chicago cGMP facility, a special lab designed for processing cells for clinical therapy such as transplant. While the pancreas is being processed, the patient is being prepared for the transplant procedure.
Once both the cells and the patient are ready, the patient goes to interventional radiology instead of the operating room. Here, the patient receives conscious sedation and numbing medication- they are not put to sleep but relaxed. Then, the radiologist accesses a big vein in the liver (like an IV) and the cells, mixed in a special transplant solution, flow into the liver (small catheter is introduced into the portal vein). This procedure usually takes under an hour and once complete, patients return to their rooms after a short stop in the recovery area and are able to eat that same day. Most patients are ready to go home after 1-2 days in the hospital.
After the procedure, the transplanted islets help diabetic patients restore proper glucose control, prevent life-threatening severe hypoglycemic episodes and ultimately remove the need for insulin supplementation.
Research related to the pancreatic islet transplantation
We have been working on islet cell research through Phase 1/2 and 3 studies that have successfully been carried out at The University of Chicago, see Studies, Publications.and Patient stories
Another project we are working on, is a Biological License Application (BLA) for islet cell as a biological product. It is under preparation in our center for submission to the FDA. Since pancreatic islet cell transplants performed as a research procedure are very expensive, we are very limited in the number of transplants we can offer patients due to limited funding. With BLA approval from FDA, we could benefit our diabetic patients by offering Islet Transplantation as a standard of care procedure that is reimbursed by medical insurance.
In the meantime, we have just initiated a new clinical study where we will transplant islets into a Sernova Cell Pouch™ that is implanted into the abdominal muscles. If you are interested and would like to find out more details, go to Sernova/JDRF study.
We are always seeking additional research funding to continue optimization and efficiency of the islet transplant procedure, protecting patients from diabetes for longer periods of time, limiting the need for immunosuppressive medication, limiting side effects and reducing the necessary number of islets and number of transplants.
Closer look at Pancreatic Islet Transplantation
Islet Transplantation as a Minimally Invasive Procedure
Islet transplantation requires neither major surgery, nor general anesthesia.
Instead, while the patient is under local anesthesia, an interventional radiologist uses the guidance of ultrasound and flouroscopy to place a small catheter percutaneously into the portal vein in the liver. The islets, that are suspended in a special transplant solution and placed into a plastic infusion bag, are then infusedvia gravity through the small catheter into the portal vein. (movie below). The procedure takes 30-60 minutes. Afterwards, the patient is taken to the recovery room for a few hours and then to a private room for an evening meal. Patients are kept for an additional day or two to adjust immunosuppression and other medications as well as observe for possible complications, including a 10% chance of intra-abdominal bleeding that could require blood transfusion.
Alternatively, when necessary due to an inability to access the portal vein in interventional radiology, there is a small chance the the portal vein may be accessed surgically via a mini-laparotomy under general anesthesia in the operating room. This may extend the recovery period.