Superiority of Small Islets in Human Islet Transplantation

  1. Roger Lehmann1,
  2. Richard A. Zuellig1,
  3. Patrick Kugelmeier23,
  4. Philipp B. Baenninger1,
  5. Wolfgang Moritz34,
  6. Aurel Perren5,
  7. Pierre-Alain Clavien5,
  8. Markus Weber34 and
  9. Giatgen A. Spinas16
  1. 1Department of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland
  2. 2Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland
  3. 3Zurich Center for Integrative Human Physiology, Zurich, Switzerland
  4. 4Department of Visceral Surgery, University Hospital Zurich, Zurich, Switzerland
  5. 5Department of Pathology, University Hospital Zurich, Zurich, Switzerland
  6. 6Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
  1. Address correspondence and reprint requests to R. Lehmann, MD, Head of Clinical Islet Transplantation Program, Department of Endocrinology and Diabetes, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. E-mail: roger.lehmann{at}usz.ch

Abstract

Many factors influence the outcome of islet transplantation. As islets in the early posttransplant setting are supplied with oxygen by diffusion only and are in a hypoxic state in the portal system, we tested whether small human islets are superior to large islets both in vitro and in vivo. We assessed insulin secretion of large and small islets and quantified cell death during hypoxic conditions simulating the intraportal transplant environment. In the clinical setting, we analyzed the influence of transplanted islet size on insulin production in patients with type 1 diabetes. Our results provide evidence that small islets are superior to large islets with regard to in vitro insulin secretion and show a higher survival rate during both normoxic and hypoxic culture. Islet volume after 48 h of hypoxic culture decreased to 25% compared with normoxic culture at 24 h due to a preferential loss of large islets. In human islet transplantation, the isolation index (islet volume as expressed in islet equivalents/islet number), or more simply the islet number, proved to be more reliable to predict stimulated C-peptide response compared with islet volume. Thus, islet size seems to be a key factor determining human islet transplantation outcome.

Footnotes

  • R.L. and R.A.Z. contributed equally to this work.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted November 23, 2006.
    • Received June 7, 2006.
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