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Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells
Authors:J?B?Choi  H?Uchino  K?Azuma  N?Iwashita  Y?Tanaka  H?Mochizuki  M?Migita  T?Shimada  R?Kawamori  Email author" target="_blank">H?WatadaEmail author
Institution:(1) Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan;(2) Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan;(3) Department of Biochemistry and Molecular Biology, Division of Gene Therapy, Research Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan
Abstract:Aims/hypothesis Bone marrow cells contain at least two distinct types of stem cells which are haematopoietic stem cells and mesenchymal stem cells. Both cells have the ability to differentiate into a variety of cell types derived from all three germ layers. Thus, bone marrow stem cells could possibly be used to generate new pancreatic beta cells for the treatment of diabetes. In this study, we investigated the feasibility of bone marrow-derived cells to differentiate into beta cells in pancreas.Methods Using green fluorescent protein transgenic mice as donors, the distribution of haematogenous cells in the pancreas was studied after bone marrow transplantation.Results In the pancreas of green fluorescent protein chimeric mice, green fluorescent protein-positive cells were found in the islets, but none of these cells expressed insulin. Previous data has suggested that tissue injury can recruit haematopoietic stem cells or their progeny to a non-haematopietic cell fate. Therefore, low-dose streptozotocin (30 or 50 mg/kg on five consecutive days) was injected into the mice 5 weeks after bone marrow transplantation, but no green fluorescent protein-positive cells expressing insulin were seen in the islets or around the ducts of the pancreas.Conclusions/interpretation Our data suggests that bone marrow-derived cells are a distinct cell population from islet cells and that transdifferentiation from bone marrow-derived cells to pancreatic beta cells is rarely observed.Abbreviations STZ streptozotocin - EGFP enhanced green fluorescent protein - GP guinea-pig - vWF von Willebrand Factor - BrdU bromodeoxyuridine - GFP green fluorescent protein - IPGTT Intraperitoneal glucose tolerance test
Keywords:Regeneration  regeneration therapy  insulin  islet  stem cell  haematopoietic stem cell  mescenchymal stem cell  bone marrow
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