Recruitment of Bone Marrow-Derived Endothelial Cells to Sites of Pancreatic β-Cell Injury

  1. Vikram Mathews1,
  2. Piia T. Hanson1,
  3. Eric Ford2,
  4. Jun Fujita3,
  5. Kenneth S. Polonsky2 and
  6. Timothy A. Graubert1
  1. 1Department of Internal Medicine, Division of Oncology, Stem Cell Biology Section, Washington University, St. Louis, MO
  2. 2Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, Washington University, St. Louis, MO
  3. 3Kyoto Prefecture University of Medicine, 1st Department of Internal Medicine, Kyoto, Japan
  1. Address correspondence and reprint requests to Timothy Graubert, MD, Washington University School of Medicine, Division of Oncology, Stem Cell Biology Section, Campus Box 8007, 660 South Euclid Ave., St. Louis, MO 63110. E-mail: graubert{at}medicine.wustl.edu

Abstract

Endothelial progenitor cells (EPCs) are detectable in the blood and bone marrow throughout life. These cells contribute to new blood vessel formation (neovascularization) in physiological states such as wound healing and in pathological states such as tumor angiogenesis. We hypothesized that bone marrow-derived EPCs could play a role in the response to pancreatic islet cell injury. We used a murine model of experimentally induced β-cell injury followed by transplantation with genetically marked bone marrow cells. Bone marrow-derived cells were detectable throughout the pancreas after transplantation. Whereas the total number of bone marrow-derived cells in the pancreas decreased over time, the frequency of endothelial cells (of both donor and recipient origin) increased after transplantation in the animals in which β-cell injury had been induced. There was no evidence in this model that bone marrow-derived cells differentiated into insulin-expressing cells. This study provides evidence that bone marrow-derived EPCs are recruited to the pancreas in response to islet injury. EPC-mediated neovascularization of the pancreas could in principle be exploited to facilitate the recovery of non-terminally injured β-cells or to improve the survival and/or function of islet allografts.

Footnotes

    • Accepted September 26, 2003.
    • Received June 11, 2003.
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