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Failure of Transplanted Bone Marrow Cells to Adopt a Pancreatic ß-Cell Fate

¹ Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden
² Department of Physiological Sciences, Lund University, Lund Sweden
³ Department of Developmental Biology, Hagedorn Research Institute, Copenhagen, Denmark

Address correspondence and reprint requests to Sten Eirik W. Jacobsen, MD, PhD, Hematopoietic Stem Cell Laboratory, Lund University, BMC, B10, SE-221 84 Lund, Sweden. E-mail: sten.jacobsen{at}stemcell.lu.se

Key Words: GFP, green fluorescence protein • Nkx6.1, homeodomain protein • Pdx-1, pancreatic duodenal homeobox factor-1

Recent studies in normal mice have suggested that transplanted bone marrow cells can transdifferentiate into pancreatic ß-cells at relatively high efficiency. Herein, adopting the same and alternative approaches to deliver and fate map-transplanted bone marrow cells in the pancreas of normal as well as diabetic mice, we further investigated the potential of bone marrow transplantation as an alternative approach for ß-cell replacement. In contrast to previous studies, transplanted bone marrow cells expressing green fluorescence protein (GFP) under the control of the mouse insulin promoter failed to express GFP in the pancreas of normal as well as diabetic mice. Although bone marrow cells expressing GFP under the ubiquitously expressed ß-actin promoter efficiently engrafted the pancreas of normal and hyperglycemic mice, virtually all expressed CD45 and Mac-1/Gr-1, demonstrating that they adopt a hematopoietic rather than ß-cell fate, a finding further substantiated by the complete absence of GFP⁺ cells expressing insulin and the ß-cell transcription factors pancreatic duodenal homeobox factor-1 and homeodomain protein. Thus, transplanted bone marrow cells demonstrated little, if any, capacity to adopt a ß-cell fate.

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