Islet transplantation for Type 1 diabetes: where are we now?

Abstract

Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in Type 1 diabetics without the surgical complications associated with vascularized pancreas transplantation. The advances made in this field over the past decade have dramatically improved patient outcomes, and the procedure is now transitioning from an experimental treatment to a clinical reality. Nonetheless, a number of important issues continue to hamper the success of islet transplantation and must be addressed before there is widespread clinical acceptance. These include the relative inefficiency of the islet isolation process, the progressive loss of islet function over time and the need for multiple donors to achieve insulin independence. Here, we discuss the current status of islet transplantation and examine its future as a treatment for Type 1 diabetes.

Keywords:

• glycemic control
• hypoglycemic unawareness
• immunosuppression
• insulin independence
• islet transplantation
• transplant site
• Type 1 diabetes

Financial & competing interests disclosure

AM Posselt has been supported by the following NIH Grants: 1R01DK098581-01A1 (NIH), 1U01DK085531-01, 3U01DK088531-01S1, ITN-039ST, U01-DK066013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pancreatic islet transplantation is a minimally invasive, alternative to pancreas transplantation that can achieve insulin independence and improved glycemic control without the risks associated with vascularized whole organ transplantation. Though still considered experimental, islet transplantation is likely to become a clinically approved, reimbursable procedure in the near future.

• Although islet transplantation is able to achieve short-term insulin independence, current long-term clinical outcomes are somewhat worse than vascularized pancreas transplants as many patients lose islet.

• Careful processing and donor selection are crucial to obtaining islet yields required to achieve insulin independence from a single donor.

• Increased immunosuppression at the time of initial islet infusion reduces early islet loss and improves graft survival. T-cell depletion, anti-TNF-α therapies and minimization of islet-toxic agents has significantly increased the number of recipients who achieve durable insulin independence.

• Most of the benefits of islet transplantation, such as improved glycemic control and elimination of hypoxic episodes, can be achieved without insulin independence.

• Research into encapsulation and alternative sites of islet implantation may further improve islet transplant outcomes and applicability by reducing blood-mediated islet destruction, facilitating surveillance of transplanted cells and allowing use of xenogeneic or stem cell-derived islets without the need for immunosuppression.

Notes