Islet cell transplantation

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Islet cell transplantation
Microscopic image of an islet of Langerhans (lighter area) surrounded by exocrine pancreas tissue (darker staining).
MeSHD016381

Islet transplantation is the

transplantation of isolated islets from a donor pancreas into another person. It is a treatment for type 1 diabetes.[1] 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

immunosuppressant drugs are used. A study from 2005 showed that islet transplantation has progressed to the point that 58% of the people were insulin independent one year after the operation.[3] A review published 2016 reported a 50 – 70% rate of insulin independence after five years, in five studies from leading transplant centers published 2005 – 2012.[4]

In the period from 1999 to 2004, 471 people with type 1 diabetes received islet transplants at 43 institutions worldwide.[5]

Donislecel (Lantidra) allogeneic (donor) pancreatic islet cellular therapy was approved for medical use in the United States in June 2023.[6]

History

The concept of islet transplantation is not new.

Charles Pybus (1882–1975) attempted to graft pancreatic tissue to cure diabetes.[citation needed
]

Goals

The goal of islet transplantation is to infuse enough islets to control the

nerve or eye damage, a successful transplant may reduce the risk of these complications. But a transplant recipient will need to take immunosuppressive drugs that stop the immune system from rejecting the transplanted islets.[citation needed
]

Newer studies have focused their attention towards reducing severe hypoglycemic events, a life-threatening state in type 1 diabetes, rather than focus on removing the need for insulin injections entirely.[8][9]

Procedure

The process of islet transplantation (illustration by Giovanni Maki).

Researchers use a mixture of highly purified enzymes (

exocrine tissue
and debris in a process called purification.

During the transplant, a

ultrasound and radiography to guide placement of a catheter through the upper abdomen and into the portal vein of the liver. The islets are then infused through the catheter into the liver. The person will receive a local anesthetic
. If a person cannot tolerate local anesthesia, the surgeon may use general anesthesia and do the transplant through a small incision. Possible risks of the procedure include bleeding or blood clots.

It takes time for the islets to attach to new blood vessels and begin releasing insulin. The doctor will order many tests to check blood glucose levels after the transplant, and insulin may be needed until control is achieved.

  • Radiographic image of the portal vein and its branches in the transplant recipient before infusion of isolated islets.
    Radiographic image of the portal vein and its branches in the transplant recipient before infusion of isolated islets.
  • Post-transplant radiographic image of the recipient's portal tree.
    Post-transplant radiographic image of the recipient's portal tree.

Immunosuppression

The Edmonton protocol uses a combination of immunosuppressive drugs, including daclizumab (Zenapax), sirolimus (Rapamune) and tacrolimus (Prograf). Daclizumab is given intravenously right after the transplant and then discontinued. Sirolimus and tacrolimus, the two main drugs that keep the immune system from destroying the transplanted islets, must be taken for life.[citation needed]

Limitations

While significant progress has been made in the islet transplantation field,

renal function. For the person with diabetes, renal function is a crucial factor in determining long-term outcome, and calcineurin inhibitors (tacrolimus and ciclosporin) are significantly nephrotoxic. Thus, while some people with a pancreas transplant tolerate the immunosuppressive agents well, and for such people diabetic nephropathy can gradually improve, in other people the net effect (decreased risk due to the improved blood glucose control, increased risk from the immunosuppressive agents) may worsen kidney function. Indeed, Ojo et al. have published an analysis indicating that among people receiving other-than-kidney allografts, 7%–21% end up with kidney failure as a result of the transplant and/or subsequent immunosuppression.[12]

Another limitation to the islet transplantation process is the inflammatory response of the liver. Dr. Melena Bellin is an associate professor of pediatric endocrinology and surgery and director of research for the islet autotransplant program at the University of Minnesota Medical Center and Masonic Children's Hospital. Her research centers on making islet transplants safer and more effective for type one diabetics. The process of infusing islet cells into the liver can trigger an inflammatory response in the body. This reaction leads to a large amount of the newly transplanted islets being destroyed. Losing islet cells decreases the probability of successful insulin production and increases the likelihood of type one diabetes developing again in the patient. Dr. Bellin is currently testing two anti-inflammatory drugs that are already on the market to see if they may be useful in preventing inflammation that destroys islet cells.[13]

References

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  2. PMID 12928769
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  3. PMID 15848704
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  4. S2CID 28784928
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  5. PMID 15912095
    .
  6. ^ "FDA Approves First Cellular Therapy to Treat Patients with Type 1 Diabetes". U.S. Food and Drug Administration (FDA) (Press release). 28 June 2023. Retrieved 28 June 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  7. PMID 30505878
    .
  8. PMID 27208344
    .
  9. S2CID 22996728
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  10. S2CID 1307522
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  11. PMID 14633816. Full text
  12. S2CID 12270800
    .
  13. ^ Brody, Barbara. "Making Islet Cell Transplants Safer". Diabetes Forecast.
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