Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigens, CD34
  • Cell Count
  • Cell Movement
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Fluorouracil
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperglycemia
  • Mice
  • Mice, Inbred C57BL

MeSH Major

  • Bone Marrow
  • Diabetes Mellitus, Experimental
  • Endothelial Cells
  • Hematopoietic Stem Cells
  • Stem Cells

abstract

  • Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

publication date

  • 2013

has subject area

  • Animals
  • Antigens, CD34
  • Bone Marrow
  • Cell Count
  • Cell Movement
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Diabetes Mellitus, Experimental
  • Endothelial Cells
  • Fluorouracil
  • Hematopoietic Stem Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hyperglycemia
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3610687

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0060357

PubMed ID

  • 23555959

Additional Document Info

start page

  • e60357

volume

  • 8

number

  • 3