Hematopoietic Stem Cells Derived From Adult Donors Are Not a Source of Pancreatic β-Cells in Adult Nondiabetic Humans

  1. Alexandra E. Butler1,
  2. Andrew Huang1,
  3. P. Nagesh Rao2,
  4. Anil Bhushan1,
  5. William J. Hogan3,
  6. Robert A. Rizza4 and
  7. Peter C. Butler1
  1. 1Larry L. Hillblom Islet Research Center, University of California Los Angeles, Los Angeles, California
  2. 2Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California
  3. 3Division of Hematology, Mayo Clinic, Rochester, Minnesota
  4. 4Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota
  1. Address correspondence and reprint requests to Peter C. Butler, Division of Endocrinology, University of California Los Angeles, Larry L. Hillblom Islet Research Center, 900 Veteran Ave., 24-130 Warren Hall, UCLA, Los Angeles, CA 90095-7073. E-mail: pbutler{at}mednet.ucla.edu

Abstract

OBJECTIVE—Type 1 and type 2 diabetes are characterized by an ∼98 and ∼65% loss of pancreatic β-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility of promoting β-cell replacement and/or regeneration. Islet transplantation has been explored, but it does not provide long-term insulin independence. One possible source of β-cell regeneration is hematopoietic stem cells. In mice, there are conflicting data as to whether hematopoietic stem cells contribute to pancreatic β-cells. We sought to establish whether hematopoietic stem cells (derived from adult donors) transdifferentiate into pancreatic β-cells in adult humans.

RESEARCH DESIGN AND METHODS—We addressed this in 31 human pancreata obtained at autopsy from hematopoietic stem cell transplant recipients who had received their transplant from a donor of the opposite sex.

RESULTS—Whereas some donor-derived cells were observed in the nonendocrine pancreata, no pancreatic β-cells were identified that were derived from donor hematopoietic stem cells, including two cases with type 2 diabetes.

CONCLUSIONS—We conclude that hematopoietic stem cells derived from adult donors contribute minimally to pancreatic β-cells in nondiabetic adult humans. These data do not rule out the possibility that hematopoietic stem cells contribute to pancreatic β-cells in childhood or in individuals with type 1 diabetes.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 24 April 2007. DOI: 10.2337/db06-1385.

  • 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 April 17, 2007.
    • Received September 29, 2006.
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  1. Published online before print April 24, 2007, doi: 10.2337/db06-1385 Diabetes July 2007 vol. 56 no. 7 1810-1816
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