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

¹ Larry L. Hillblom Islet Research Center, University of California Los Angeles, Los Angeles, California
² Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, California
³ Division of Hematology, Mayo Clinic, Rochester, Minnesota
⁴ Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota

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

Abbreviations: FISH, fluorescent in situ hybridization; FTIC, fluorescein isothiocyanate

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

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