title: Endothelial colony-forming cells ameliorate endothelial dysfunction via secreted factors following ischemia-reperfusion injury.
abstract: Damage to endothelial cells contributes to acute kidney injury (AKI) by leading to impaired perfusion. Endothelial colony-forming cells (ECFC) are endothelial precursor cells with high proliferative capacity, pro-angiogenic activity, and in vivo vessel forming potential. We hypothesized that ECFC may ameliorate the degree of AKI and/or promote repair of the renal vasculature following ischemia-reperfusion (I/R). Rat pulmonary microvascular endothelial cells (PMVEC) with high proliferative potential were compared with pulmonary artery endothelial cells (PAEC) with low proliferative potential in rats subjected to renal I/R. PMVEC administration reduced renal injury and hastened recovery as indicated by serum creatinine and tubular injury scores, while PAEC did not. Vehicle-treated control animals showed consistent reductions in renal medullary blood flow (MBF) within 2 h of reperfusion, while PMVEC protected against loss in MBF as measured by laser Doppler. Interestingly, PMVEC mediated protection occurred in the absence of homing to the kidney. Conditioned medium (CM) from human cultured cord blood ECFC also conveyed beneficial effects against I/R injury and loss of MBF. Moreover, ECFC-CM significantly reduced the expression of ICAM-1 and decreased the number of differentiated lymphocytes typically recruited into the kidney following renal ischemia. Taken together, these data suggest that ECFC secrete factors that preserve renal function post ischemia, in part, by preserving microvascular function.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, Indiana; and.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Collett
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, Indiana; and.
authors.forename: Purvi
authors.initials: P
authors.lastname: Mehrotra
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, Indiana; and.
authors.forename: Allison
authors.initials: A
authors.lastname: Crone
authors.affiliation: Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: W Christopher
authors.initials: WC
authors.lastname: Shelley
authors.affiliation: Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University, Indianapolis, Indiana; and dpbasile@iupui.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Basile
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D000818:Animals; D001783:Blood Flow Velocity; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; C573420:ICAM1 protein, human; D018799:Intercellular Adhesion Molecule-1
keywords: angiogenesis; endothelial progenitor; hemodynamics; regeneration