title: Changes in the frequency and in vivo vessel-forming ability of rhesus monkey circulating endothelial colony-forming cells across the lifespan (birth to aged).
abstract: BACKGROUND
  We have identified a novel hierarchy of human endothelial colony-forming cells (ECFCs) that are functionally defined by their proliferative and clonogenic potential and in vivo vessel-forming ability. The rhesus monkey provides an excellent model in which to examine the changes in circulating concentrations and functions of ECFCs since this nonhuman primate possesses a long lifespan and has been used extensively to model age-related processes that occur in humans.
  
  
  RESULTS
  Endothelial cells (ECs) derived from rhesus monkey ECFCs share a cell-surface phenotype similar to human cord blood ECFCs, rapidly form capillary-like structures in vitro, and form endothelial-lined vessels in vivo upon implantation in immunodeficient mice in an age-dependent manner. Of interest, although ECFCs from the oldest monkeys formed capillary-like structures in vitro, the cells failed to form inosculating vessels when implanted in vivo and displayed a deficiency in cytoplasmic vacuolation in vitro; a critical first step in vasculogenesis.
  
  
  CONCLUSIONS
  Utilizing previously established clonogenic assays for defining different subpopulations of human ECFCs, we have shown that a hierarchy of ECFCs, identical to human cells, can be isolated from the peripheral blood of rhesus monkeys, and that the frequency of the circulating cells varies with age. These studies establish the rhesus monkey as an important preclinical model for evaluating the role and function of circulating ECFCs in vascular homeostasis and aging.
  
  
  METHODS
  Peripheral blood samples were collected from 40 healthy rhesus monkeys from birth to 24 years of age for ECFC analysis including immunophenotyping, clonogenic assays, and in vivo vessel formation.
authors.affiliation: Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: W Chris
authors.initials: WC
authors.lastname: Shelley
authors.forename: Alyssa C
authors.initials: AC
authors.lastname: Leapley
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Critser
authors.forename: Pingyu
authors.initials: P
authors.lastname: Zeng
authors.forename: Daniel
authors.initials: D
authors.lastname: Prater
authors.forename: David A
authors.initials: DA
authors.lastname: Ingram
authors.forename: Alice F
authors.initials: AF
authors.lastname: Tarantal
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D016130:Immunophenotyping; D008253:Macaca mulatta; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D010641:Phenotype; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D014617:Vacuoles / Q000502:physiology
chemical_list: D015415:Biomarkers