title: Impaired development and dysfunction of endothelial progenitor cells in type 2 diabetic mice.
abstract: OBJECTIVE
  Dysfunction of circulating endothelial progenitor cells (EPCs) has been shown to affect the development of microvascular diseases in diabetes patients. The aim of this study was to elucidate the development and mechanical dysfunction of EPCs in type 2 diabetes (T2D).
  
  
  METHODS
  The colony-forming capacity of EPCs and differentiation potential of bone marrow (BM) c-Kit(+)/Sca-I(+) lineage-negative mononuclear cells (KSL) were examined in T2D mice, db/db mice and KKAymice, using EPC colony-forming assay (EPC-CFA).
  
  
  RESULTS
  T2D mice had fewer BM stem/progenitor cells, and proliferation of KSL was lowest in the BM of db/db mice. In T2D mice, the frequency of large colony-forming units (CFUs) derived from BM-KSL was highly reduced, indicating dysfunction of differentiation into mature EPCs. Only a small number of BM-derived progenitors [CD34(+) KSL cells], which contribute to the supply of EPCs for postnatal neovascularization, was also found. Furthermore, in terms of their plasticity to transdifferentiate into various cell types, BM-KSL exhibited a greater potential to differentiate into granulocyte macrophages (GMs) than into other cell types.
  
  
  CONCLUSIONS
  T2D affected EPC colony formation and differentiation of stem cells to mature EPCs or haematopoietic cells. These data suggest opposing regulatory mechanisms for differentiation into mature EPCs and GMs in T2D mice.
authors.affiliation: Department Regenerative Medicine, Tokai University of Medicine, Kobe, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsukada
authors.affiliation: Department Regenerative Medicine, Tokai University of Medicine, Kobe, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Yun
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Kang
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: D Y
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: S T
authors.initials: ST
authors.lastname: Ji
authors.affiliation: Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Immunoregulatory Therapeutics Group in Brain Busan 21 Project, Pusan National University, Yangsan, Republic of Korea. Electronic address: smkwon323@pusan.ac.kr.
authors.forename: S-M
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Department Regenerative Medicine, Tokai University of Medicine, Kobe, Japan; Stem Cell Translational Research Laboratory, Center For Developmental Biology, RIKEN, Kobe, Japan; Kobe Institute of Biomedical Research and Innovation, Kobe, Japan. Electronic address: asa777@aol.com.
authors.forename: T
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: Colony-forming assay; Diabetes; Differentiation; Endothelial progenitor cells; Granulocyte macrophages