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Abstract

This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.

Oxygenation of the Intraportally Transplanted Pancreatic Islet

“…To prevent diabetes in this patient, >10% of the islet mass (~100 thousand IEs, or 1,429 IEs per kgBW) would need to remain following partial islet destruction or pancreatectomy. However, if this patient were a type 1 diabetic and a candidate for allo-IT, empirical clinical data would indicate that the minimum islet dose required to achieve insulin independence would be >60% of their original islet mass (~630,000 IEs or ~9,000 IEs per kgBW) [1–3, 6, 8] and on average would be probably higher at >70–90% (~700,000–910,000 IEs or ~10,000–13,000 IEs per kgBW) [1–3, 5, 6, 67, 68], even with the most potent induction immunosuppression currently available [69]. If this patient was a candidate for near-total or total pancreatectomy followed by auto-IT, then >35% of their original islet mass (~350,000 IEs or ~5,000 IEs per kgBW) may be required to prevent overt diabetes [70–72], and the rate of insulin independence may only be ~50–70% at 3–5 years after IT [71, 72].…”

“…This requirement of multiple pancreas donors is a major limitation that prohibits widespread availability of IT due to increased costs and clinical risk associated with multiple procedures, placing an additional strain on an already limited donor pancreas supply. In the mid-2000s, new trials were undertaken to establish protocols that enable successful IT using islets from a single donor pancreas [7, 8]. Newer induction immunosuppressive agent combinations [T-cell-depleting antibody (anti-CD3 antibody, alemtuzumab, or antithymocyte globulin) and a tumor necrosis factor alpha (TNF- α ) inhibitor (etanercept or infliximab)] have improved long-term diabetes reversal rates (~50% in 5 years at the most experienced centers) [9], presumably by preserving transplanted β -cell mass.…”

Correlation between β cell mass and glycemic control in type 1 diabetic recipients of islet cell graft

“…However, the degree and duration of clinical success are variable, and only 10% of recipients remain insulin-independent for 5 years (1). Normalization of hyperglycemia is sometimes achieved with a graft from one pancreas (2,3), but more often requires combined isolates from more donor organs (4)(5)(6)(7)(8); these are then injected at one or, more often, two or three time points with different intervals, each involving an additional antibody treatment (2)(3)(4)(5)(6)(7)(8). Grafts have not been standardized in terms of cellular composition and ␤ cell mass.…”

Toward Maximizing the Success Rates of Human Islet Isolation: Influence of Donor and Isolation Factors

“…Sufficient islet numIn the present study, we have analyzed the effects of donor and islet processing factors on the success rate of bers can be obtained from a single donor (11,19,62,63), but generally more than one islet preparation per recipihuman islet cell processing for transplantation performed at a single islet cell processing center. ent is required to observe insulin independence after transplantation (11,14,32,59,62). Steady progress has been obtained in recent years thanks to improved organ MATERIALS AND METHODS recovery and preservation methods (9,26,28,50), and isPancreas Procurement let isolation and purification techniques (1,22,29,52).…”