Point: Steady Progress and Current Challenges in Clinical Islet Transplantation

  1. Davide Mineo, MD, PHD1,2,
  2. Antonello Pileggi, MD, PHD1,3,
  3. Rodolfo Alejandro, MD1,4 and
  4. Camillo Ricordi, MD1,3,4,5,6,7
  1. 1Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida;
  2. 2Department of Internal Medicine and University Policlinic, Tor Vergata University, Rome, Italy;
  3. 3DeWitt-Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida;
  4. 4Department of Medicine, Division of Endocrinology, University of Miami Miller School of Medicine, Miami, Florida;
  5. 5Department of Biomedical Engineering, University of Miami Miller School of Medicine, Miami, Florida;
  6. 6Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina;
  7. 7Karolinska Institutet, Stockholm, Sweden.
  1. Corresponding author: Camillo Ricordi, ricordi{at}
  1. D.M. and A.P. equally contributed to this work.

The field of β-cell replacement therapies has evolved substantially over the last decades. The lesson learned from recent islet transplantation trials in patients with unstable type 1 diabetes is that primary goals are the achievement of stable, normalized glycemic control in the absence of severe hypoglycemic episodes with improvement of quality of life and the prevention of progressive, chronic diabetes complications. Insulin independence, although desirable, should not be considered the main objective, particularly in light of the sustained positive effects achieved even with a “marginal” functional islet mass via restoration of C-peptide secretion and reduction of insulin requirements. As present limitations of islet transplantation are progressively overcome, the clinical application will greatly expand from the currently limited indication in controlled clinical research trials to more widely available cellular therapies and regenerative medicine solutions that will eventually be offered as standard treatment to the majority of patients with insulin-requiring diabetes.

Vantyghem et al. (1) in the article in this issue of Diabetes Care evaluated the predictive value of primary graft function on long-term clinical outcomes of islet transplantation alone (ITA). Surrogate measures have been proposed to monitor or predict β-cell function, but they are not yet fully validated (24). In this report, the use of the β-score in the early posttransplant period allowed to quantify primary graft function that, when “optimal,” was associated with prolonged graft survival and better metabolic control following islet transplantation (1). In agreement with previous reports using the “Edmonton Protocol” (510), this trial resulted in a significant improvement of metabolic control and long-term graft function (∼70% having measurable C-peptide at 5 years). Importantly, the investigators also showed prolonged insulin independence in 57% of the patients at 5 years, with the subjects with optimal primary graft …

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