Limitations
While significant progress has been made in the islet transplantation field, many obstacles remain that currently preclude its widespread application. Two of the most important limitations are the currently 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 the agents used in these treatments are expensive and may increase the risk for specific malignancies and opportunistic infections. In addition, and somewhat ironically, the most commonly used agents (like calcineurin inhibitors and rapamycin) are also known to impair normal islet function and/or insulin action. Further, like all medications, the agents have other associated toxicities, with side effects such as oral ulcers, peripheral edema, anemia, weight loss, hypertension, hyperlipidemia, diarrhea and fatigue. Perhaps of greatest concern to the patient and physician is the harmful effect of certain widely employed immunosuppressive agents on renal function. For the patient 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 patients with a pancreas transplant tolerate the immunosuppressive agents well, and for such patients diabetic nephropathy can gradually improve, in other patients 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 patients receiving other-than-kidney allografts, 7%–21% end up with renal failure as a result of the transplant and/or subsequent immunosuppression.
Seen another way, patients with heart, liver, lung, or kidney failure have a dismal prognosis for survival, so the toxicity associated with immunosuppression is warranted (the benefits of graft survival outweigh the risks associated with the medications). But for the subset of patients with diabetes and preserved kidney function, even those with long-standing and difficult-to-control disease, the prognosis for survival is comparatively much better. In addition to the immunosuppressive toxicities, other risks are associated with the islet transplant procedure itself, including intra-abdominal hemorrhage following the transplant, and portal vein thrombosis. The fact that there is already a good alternative to islet transplantation (i.e. the modern intensive insulin regimen) forces us to regard any newer, riskier interventions with a critical eye.
Like all transplantation therapies, islet transplantation is also handicapped by the limited donor pool. The numbers are striking; at least 1 million Americans have type 1 diabetes mellitus, and only a few thousand donor pancreata are available each year. To circumvent this organ shortage problem, researchers continue to look for ways to "grow" islets—or at least cells capable of physiologically regulated insulin secretion—in vitro, but currently only islets from cadaveric donors can be used to restore euglycemia. Further exacerbating the problem (and unlike kidney, liver, and heart transplants, where only one donor is needed for each recipient) most islet transplant patients require islets from two or more donors to achieve euglycemia. Lastly, the current methods for islet isolation need improvement, since only about half of attempted isolations produce transplant-ready islets.
While islet transplantation research has made important progress and the success stories are encouraging, the long-term safety and efficacy of the procedure remain unclear. Other concerns relating to the field include questions about the impact of having insulin-producing foreign cells within the hepatic parenchyma, the long-term consequences of elevated portal pressures resulting from the islet infusion, and the fact that islet recipients can be sensitized against donor tissue types, making it more difficult to find a suitable donor should another life-saving transplant be required in the future. Also, very few islet transplant recipients have remained euglycemic without the use of any exogenous insulin beyond four years post-transplant. Thus, while most islet recipients achieve better glycemia control and suffer less serious hypoglycemia, islet transplantation continues to fall short of the definitive diabetes cure.
Read more about this topic: Islet Cell Transplantation
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—H.L. (Henry Lewis)