Islet cell transplantation

Islet transplantation is the transplantation of isolated islets from a donor pancreas into another person. 

Once transplanted, the islets begin to produce insulin, actively regulating the level of glucose in the blood.

Islets are usually infused into the person’s liver.

If the cells are not from a genetically identical donor the person’s body will recognize them as foreign and the immune system will begin to attack them as with any transplant rejection. 

74% of patients are insulin independent 2 years after autologous transplantation of islets via portal vein infusion.

For an average-size person (70 kg), a typical transplant requires about one million islets, isolated from two donor pancreases. 

Success rate has been improved by transplanting a higher mean islet mass islet equivalents prepared from 2-4 donor pancreases and using glucocorticosteroid free immunosuppression.

The most common site for islet cell infusion is the liver via the portal vein.

Intrahepatic islets are unable to release glucagon during hypoglycemia.

A mixture of highly purified enzymes (Collagenase) to isolate islets from the pancreas of a deceased donor. 

Collagenase solution is injected into the pancreatic duct which runs through the head, body and tail of the pancreas. 

The enzyme solution causes distension of the pancreas, which is subsequently cut into small pieces and transferred into a chamber, where digestion takes place until the islets are liberated and removed from the solution. 

The islets are then infused through the catheter into the liver. 

Immunosuppression uses a combination of immunosuppressive drugs: including daclizumab, sirolimus and tacrolimus.

Currently there is inadequate means for preventing islet rejection, and the limited supply of islets for transplantation. 

Current immunosuppressive regimens are capable of preventing islet failure for months to years, but theyb may increase the risk for specific malignancies and opportunistic infections. 

The  most commonly used agents, like calcineurin inhibitors and rapamycin, are also known to impair normal islet function and/or insulin action. 

These agents have other associated toxicities, with side effects such as oral ulcers, peripheral edema, anemia, weight loss, hypertension, hyperlipidemia, diarrhea and fatigue, and impaired renal function. 

The process of infusing islet cells into the liver can trigger an inflammatory response leading to a large amount of the newly transplanted islets being destroyed. 

Isolated islets are then separated from the exocrine tissue/debris in a process called purification.

During the transplant ultrasound and radiography guide placement of a catheter through the upper abdomen and into the portal vein of the liver. 

For chronic pancreatitis with auto transplantation and total pancreatectomy, results in a 73% pain relief and 80% insulin independence, with more than 70% of patients receiving >2500 IEQ/kg insulin independent 2 years after transplant.

For chronic pancreatitis patients treated with auto transplantation and pancreatectomy no patients develop diabetes when insulin free for 2 years or more after transplant.

For chronic pancreatitis limited pancreatic resections diminish the pancreatic reserve and decrease chance of future salvage of islet cells.

For chronic pancreatitis pancreatic drainage procedures limit the ability to obtain high islet cell yields because of pancreatic duct cannulation and collagenase distension are more difficult.

For chronic pancreatitis mild fibrosis is associated with a high chance of success with auto transplantation.

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