title: Bone marrow transplantation stimulates pancreatic β-cell replication after tissue damage.
abstract: Bone marrow transplantation has been shown to normalize hyperglycemia but the mechanisms underlying pancreatic β-cell regeneration remain elusive. Here, we investigate the capacity of transplanted bone marrow cells to engraft into the pancreas, to adopt an endothelial cell phenotype and to stimulate β-cell regeneration after islet damage. Genetically marked whole bone marrow from Tie2-Cre/ZEG mice was transplanted into lethally irradiated wild-type mice. The fate of the transplanted cells, as well as blood glucose levels and β-cell mass dynamics, was investigated in normal and hyperglycemic recipient mice. Bone marrow transplantation significantly increased β-cell mass and reduced the hyperglycemia of mice subjected to β-cell damage by streptozotocin (STZ). This was associated with enhanced replication of pre-existing β-cells, proportional to the degree of β-cell damage, whereas no evidence was obtained for islet neogenesis. The engrafted bone marrow-derived cells in the pancreas showed little capacity to differentiate into blood vessel endothelium but retained a myeloid cell fate. By contrast, the transplantation evoked pronounced proliferation of recipient endothelial cells. These findings illuminate an important adjuvant function of transplanted bone marrow cells in both angiogenesis and β-cell regeneration. This may have interesting clinical implications, not least for human islet transplantation endeavours, where co-transplantation of islets with bone marrow cells might represent a simple means to improve islet survival and function.
authors.affiliation: Clinical Research Center, Section of Islet pathophysiology, Lund University, Malmö, Sweden.
authors.forename: Andres H
authors.initials: AH
authors.lastname: Rosengren
authors.forename: Jalal
authors.initials: J
authors.lastname: Taneera
authors.forename: Simin
authors.initials: S
authors.lastname: Rymo
authors.forename: Erik
authors.initials: E
authors.lastname: Renström
mesh_terms: D000465:Algorithms; D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D013311:Streptozocin; D015854:Up-Regulation / Q000502:physiology
chemical_list: D013311:Streptozocin; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse