Failure of transplanted bone marrow cells to adopt a pancreatic beta-cell fate.
Recent studies in normal mice have suggested that transplanted bone marrow cells can transdifferentiate into pancreatic beta-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 beta-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 beta-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 beta-cell fate, a finding further substantiated by the complete absence of GFP(+) cells expressing insulin and the beta-cell transcription factors pancreatic duodenal homeobox factor-1 and homeodomain protein. Thus, transplanted bone marrow cells demonstrated little, if any, capacity to adopt a beta-cell fate.
Taneera
Jalal
J
Hematopoietic Stem Cell Laboratory, Lund University, Sweden.
Rosengren
Anders
A
Renstrom
Erik
E
Nygren
Jens M
JM
Serup
Palle
P
Rorsman
Patrik
P
Jacobsen
Sten Eirik W
SE
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D019070:Cell Lineage; D003921:Diabetes Mellitus, Experimental; D000077270:Exenatide; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides; D015534:Trans-Activators / Q000378:metabolism; D014688:Venoms
D018398:Homeodomain Proteins; D007328:Insulin; C491328:Nkx6-1 protein, mouse; D010455:Peptides; D015534:Trans-Activators; D014688:Venoms; C084010:pancreatic and duodenal homeobox 1 protein; D000077270:Exenatide