Overview of Islets Transplantation
Transplanting pancreatic islet cells, which are a type of cell that helps regulate sugar levels in the body, can help treat dangerously low blood sugar episodes that can’t be addressed with other medical treatments. This procedure has also successfully allowed some patients to stop the use of injected insulin, which is often necessary for people suffering from diabetes.
Compared to a solid organ pancreas transplant, an islet cell transplant is less invasive and is considered one of the safest transplant procedures available. This treatment even has the potential to cure type I diabetes, which is a condition where the body doesn’t create any insulin at all.
Currently, a lot of research is being conducted to improve the survival of these cells after they have been transplanted. Researchers have discovered that certain receptors within the islet cells – these are structures that respond to specific signals – can also improve how these cells work and survive, especially when they’re under stress from inflammation or high blood sugar levels. This is often the case following a transplant.
Anatomy and Physiology of Islets Transplantation
The pancreas is an organ that has three parts: a head, a body, and a tail. The head gets its blood from two arteries called the superior and inferior pancreaticoduodenal arteries. Meanwhile, branches from another artery, known as the splenic artery, provide blood to the body and tail. The pancreas has two key jobs. One is related to digestion (exocrine) and the other is related to producing hormones (endocrine).
The pancreas has a unique circulatory system. This links the part of the pancreas that helps with digestion (exocrine) and the part that produces hormones (endocrine), essentially letting them share resources and communicate more effectively.
The hormone-producing part of the pancreas contains clusters of cells called Islet cells. These cells give the pancreas its ability to produce hormones. Islet cells have five different types of cells, all of which make a unique hormone. Alpha cells secrete glucagon, delta cells secrete somatostatin, beta cells secrete insulin, gamma cells secrete pancreatic polypeptide, and epsilon cells secrete ghrelin. These hormones are released directly into the bloodstream when needed, in response to changes in the body.
Why do People Need Islets Transplantation
Islet cell transplantation is a procedure currently approved to help individuals suffering from Type 1 diabetes, who continuously experience low blood sugar levels that can’t be controlled with medication. Reports have shown that 50 to 70% of patients who have undergone this procedure can live without the need for insulin injections even five years post-transplant, showing the promising potential of this treatment.
However, one of the major factors stopping this from being considered a definitive cure is the need for patients to take immunosuppressant drugs for the rest of their lives to prevent the body from rejecting the transplanted cells. Recent research in mice suggests that by inhibiting a receptor called GPR44/DP2, which reduces insulin secretion when activated, the transplantation may be more successful.
To be considered for this procedure, patients need to meet the following criteria:
- Emotionally stable and able to comply with the treatment plan
- Diagnosed with Type 1 diabetes before the age of 40 and has needed insulin for over 5 years
- Age between 18 and 65
- Despite diligently administering insulin and seeking expert advice, the patient has experienced at least two episodes of symptomatic low blood sugar in the past six months
When a Person Should Avoid Islets Transplantation
Donated pancreatic islet cells, which are cells in the pancreas that produce insulin, are put into the recipient’s body through the portal system, a major vein that carries blood to the liver. However, if the pressure in the portal vein is above 20 mmHg at the start, the transplantation could be dangerous due to a high risk of blood clot formation.
Once a patient has received these new islet cells, they need to take medication for the rest of their life to stop their body from rejecting the cells, this is known as immunosuppression. If they cannot handle these medications, the transplantation cannot take place.
The transplantation cannot be performed if the patient’s body is trying to get rid of an infection – this is because the new cells do not survive well in this situation. Also, if a patient currently has a malignant tumor (cancer), they are not suitable for transplantation. The only exception is if they have had a specific type of skin cancer (either basal cell or squamous cell carcinoma) and have been cancer-free for more than five years after the tumor was removed.
Equipment used for Islets Transplantation
Islet cell transplantation is a medical procedure with different techniques and involves different kinds of tools. The list of tools I am going to describe is the most commonly used method, first developed in 1987 by a doctor named Ricordi.
These tools include:
- Two angiocatheters of 16-20 gauge (these are thin tubes inserted into a vein),
- chemicals called collagenase and a serine-protease inhibitor, which help to separate and protect the cells during the procedure,
- a special device called a Ricordi chamber, which has a filter with tiny holes,
- nine stainless steel balls,
- a device called a peristaltic pump, which moves fluids through tubes,
- a fluid called Hank’s solution,
- a heating circuit to keep everything at the right temperature,
- a chemical called Dithizone stain that helps identify certain cells,
- coils and gelatin sponges, often used to prevent bleeding, and
- imaging tools like ultrasound or fluoroscopy, which let doctors see inside your body during the procedure.
All of these tools work together to make the transplantation of islet cells as safe and effective as possible.
Who is needed to perform Islets Transplantation?
This treatment is quickly advancing as technology improves. It requires special equipment, which is why medical experts like radiologists and their teams need to be involved when the cells are infused. In the past, transplant surgeons, who are doctors specializing in organ transplant surgeries, were the main ones handling cell therapy. Today, interventional radiologists have become key players too. Interventional radiologists are doctors who use image-guided procedures to diagnose and treat diseases.
The interventional radiologists and their team can now share some of the tasks usually done by the transplant surgeons and their technologists. A technologist is someone trained to assist in technical procedures. The medical professionals who typically needed to carry out this treatment may include, but are not limited to:
- A transplant surgeon, who is a doctor specialized in transplanting organs,
- A surgical technologist, who assists the doctor during surgeries,
- A radiologist, who looks at the images taken by X-rays, CT scans, and MRIs,
- An anesthesiologist or C.R.N.A, who is responsible for making sure the patient is pain-free during the procedure, and
- A nurse, who cares for the patient before, during, and after surgery.
Preparing for Islets Transplantation
Patients who might need the treatment are first checked and identified by doctors specialized in endocrinology. If patients are found to be a good match for the treatment, they then meet with a psychologist. The psychologist checks the patient’s readiness and ability to stick with the treatment plan.
The next step involves transplant surgeons. They are skilled doctors who take the islet cells from donors who have passed away. Islet cells are unique cells in the pancreas that produce insulin, a hormone that helps control our blood sugar levels.
Once the islet cells are obtained, they are carefully separated from the rest of the pancreas tissue. This separation is done using a special mixture of enzymes and a process called density centrifugation, which helps separate the cells based on their size and weight. After this, the isolated islet cells (now called grafts) are checked to ensure their quality and quantity.
For the best possible outcome, a patient typically receives islet cells from multiple donors. By using more islet cells, doctors increase the chances that enough cells will survive in the patient’s body, boosting the chances for a successful treatment.
How is Islets Transplantation performed
The islets of Langerhans, which are clusters of cells that take part in managing blood glucose levels, are taken from a donor. First, parts of the organ including the duodenum (first part of the small intestine), spleen, lymph nodes, and excess fat are removed from around the pancreas. Following this, the pancreas is cut at the head of the organ and tubes are placed into the main pancreatic duct, an important channel in the pancreas.
The pancreas is then cleaned using a solution that has collagenase, an enzyme that breaks down proteins. The organ is cooled and then cut into smaller sections. After this, it is placed into a part of the Ricordi chamber, a special container used for processes like this. A special solution is then added into the chamber to assist with the digestion of the pancreatic tissue.
Subsequently, a solution known as Hank’s Solution is released to help manage and control the reaction. The temperature of the solution is regulated and circulated until the islets get separated from the rest of the pancreatic tissue. They are then collected and stained with a special dye called dithizone, which is then used for analysis.
The islets are then examined with a computer analysis to check if they are usable. The qualities that they look for are the purity, how well they can survive (viability), how effectively the islets can work (potency), and stability. The islets must then be transfused into the person in need within 72 hours after they are harvested, which allows for the highest chance of survival.
The volume of the islet cells being transplanted should not exceed 5 ml. These are then combined with a blood-thinner called heparin, along with a solution, usually lactated Ringer’s solution. This solution is typically used to restore fluid balance in the body.
Once this solution is prepared, it can be transplanted into the recipient in a few ways. One method involves a minimally invasive surgery to insert a tube into a vein in the intestines or stomach, this is done by transplant surgeons. Another method is guided by imaging, where a radiologist can also get access to the portal vein, which is a major vein that carries blood to the liver. Once a vein is accessed, it takes around 15 minutes to infuse the mixture of islets, heparin, and solution.
Through this process, the pressure of the portal vein is carefully monitored and maintained below 22 mmHg. Once the infusion is completed and the tube is removed from the vein, additional materials like gelatin sponges and coils are placed into the infusion site to assist with healing.
Possible Complications of Islets Transplantation
Like every surgery, there could be potential complications. One of the most common complications is the development of a clot in the portal vein, a condition known as portal vein thrombosis. A clot can result in the complete failure of the transplanted tissue. However, with the addition of a medication called heparin during the infusion process, the occurrence of life-threatening clots has become rare.
Bleeding is another common complication that can happen in about 8% of islet transplant procedures. ‘Islet’ refers to the cells in the pancreas that produce insulin. Other possible complications include infections, and issues such as pancreatic leaks, bile leaks, pancreatitis, and mycotic aneurysms which are bulges that happen in a blood vessel due to an infection. It’s also worth noting that as many as 30% of patients that undergo this surgery may need another operation.
What Else Should I Know About Islets Transplantation?
When doctors perform islet cell transplantation – a procedure where cells from a healthy pancreas are moved to a person with diabetes – the biggest challenge is the body’s initial reaction. This is known as the “instant blood mediated inflammatory reaction”, which can be described as a sudden and severe inflammation caused by the body’s immune system. This reaction causes blood cells to cluster together and form clots. To reduce the impact of this reaction and decrease the chances of the body rejecting the new cells, strong medications are used.
The main aim of islet cell transplantation is to help patients become less dependent on insulin, a hormone that regulates blood sugar levels. Depending on the center where you get the treatment, the success rate of this procedure can be different, varying from 20% to 90%. Centers with more experience in doing these infusions tend to have better success rates.
It’s also important to know that the benefits of each round of islet cell infusion don’t last forever; typically, they last about three years. After this time, a new round of infusions might be needed in order to keep patients less dependent on insulin. The good news, however, is that these transplanted islet cells can function well for up to 5 years after the infusion.
Islet cell transplantation is a procedure that’s used in hospitals and clinics today. However, scientists are continually making new discoveries and improvements, which means the procedure will continue to evolve. Over time, these improvements should lead to more consistent and longer-lasting results for patients.
