title: Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the murine oxygen-induced retinopathy model.
abstract: OBJECTIVE
  Retinopathy of prematurity (ROP) causes serious blindness because of the vasculopathy that results from the abnormal oxygen dynamics. However, the systemic kinetics of bone marrow-derived endothelial progenitor cells (BM-derived EPCs) during the "postnatal vasculogenesis " of ROP has yet to be elucidated. Thus, the authors investigated the kinetics of BM-derived EPCs using a murine oxygen-induced retinopathy (OIR) model.
  
  
  METHODS
  OIR was induced in C57BL/6J mice by continual aeration with 75% oxygen from postnatal day (P) 7 to P12 that afterward returned to normal room air.
  
  
  RESULTS
  The frequency of circulating EPCs (Sca-1(+)/c-Kit(+) cells in blood) in an OIR model estimated by FACS decreased immediately after the hyperoxic phase (P12) and then increased at the hypoxic phase (P17) compared with control. Further, EPC colony-forming assay of BM-Lin(-)/Sca-1(+) (BM-LS) cells exhibited a conversion from the predominant primitive EPC colony production at P12 to the definitive EPC colony at P17. In the OIR retinas of BM-transplanted mice with BM-LS cells of EGFP transgenic mice, there was less incorporation of GFP(+) cells into vascular structures at P12, whereas there was a drastic recruitment into the "tufts " and for the intact vasculature at P17. Moreover, the definitive EPC colony cells intravitreally injected into OIR significantly abrogated pathologic versus primitive vascular growth.
  
  
  CONCLUSIONS
  Taken together, these findings propose that the deviation of functional bioactivities of BM-derived EPCs contributing to intact vascular development under the abnormal oxygen dynamics may provide important mechanistic insight into pathologic vascular development in ROP.
authors: Departments of Regenerative Medicine Science, Tokai University School of Medicine, Isehara, Japan.
authors: Yoshihiro
authors: Y
authors: Nakagawa
authors: Haruchika
authors: H
authors: Masuda
authors: Rie
authors: R
authors: Ito
authors: Michiru
authors: M
authors: Kobori
authors: Mika
authors: M
authors: Wada
authors: Tomoko
authors: T
authors: Shizuno
authors: Atsuko
authors: A
authors: Sato
authors: Takahiro
authors: T
authors: Suzuki
authors: Kenji
authors: K
authors: Kawai
authors: Takayuki
authors: T
authors: Asahara
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000633:toxicity; D012171:Retinal Vessels / Q000166:cytology; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D049452:Green Fluorescent Proteins; D010100:Oxygen