title: Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury.
abstract: BACKGROUND
  Bone marrow-derived progenitors for both epithelial and endothelial cells have been observed in the lung. Besides mature endothelial cells (EC) that compose the adult vasculature, endothelial progenitor cells (EPC) are supposed to be released from the bone marrow into the peripheral blood after stimulation by distinct inflammatory injuries. Homing of ex vivo generated bone marrow-derived EPC into the injured lung has not been investigated so far. We therefore tested the hypothesis whether homing of EPC in damaged lung tissue occurs after intravenous administration.
  
  
  METHODS
  Ex vivo generated, characterized and cultivated rat bone marrow-derived EPC were investigated for proliferation and vasculogenic properties in vitro. EPC were tested for their homing in a left-sided rat lung transplant model mimicking a severe acute lung injury. EPC were transplanted into the host animal by peripheral administration into the femoral vein (10(6) cells). Rats were sacrificed 1, 4 or 9 days after lung transplantation and homing of EPC was evaluated by fluorescence microscopy. EPC were tested further for their involvement in vasculogenesis processes occurring in subcutaneously applied Matrigel in transplanted animals.
  
  
  RESULTS
  We demonstrate the integration of intravenously injected EPC into the tissue of the transplanted left lung suffering from acute lung injury. EPC were localized in vessel walls as well as in destructed lung tissue. Virtually no cells were found in the right lung or in other organs. However, few EPC were found in subcutaneous Matrigel in transplanted rats.
  
  
  CONCLUSIONS
  Transplanted EPC may play an important role in reestablishing the endothelial integrity in vessels after severe injury or at inflammatory sites and might further contribute to vascular repair or wound healing processes in severely damaged tissue. Therapeutic applications of EPC transplantation may ensue.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine, Pneumology Centre, Innsbruck Medical University, Austria. c.m.kaehler@i-med.ac.at
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kähler
authors.forename: Jutta
authors.initials: J
authors.lastname: Wechselberger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hilbe
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Daniela
authors.initials: D
authors.lastname: Colleselli
authors.forename: Harald
authors.initials: H
authors.lastname: Niederegger
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Boneberg
authors.forename: Gilbert
authors.initials: G
authors.lastname: Spizzo
authors.forename: Albrecht
authors.initials: A
authors.lastname: Wendel
authors.forename: Eberhard
authors.initials: E
authors.lastname: Gunsilius
authors.forename: Josef R
authors.initials: JR
authors.lastname: Patsch
authors.forename: Jürg
authors.initials: J
authors.lastname: Hamacher
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D007263:Infusions, Parenteral; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000473:pathology* / Q000601:surgery*