Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury
1 Department of Internal Medicine, Division of General Internal Medicine, Pneumology Centre, Innsbruck Medical University, Austria
2 Department of Internal Medicine, Division of General Internal Medicine, Oncology Service, Innsbruck Medical University, Austria
3 Department of Pathology, Innsbruck Medical University, Austria
4 Department of Experimental Pathology, Innsbruck Medical University, Austria
5 Biotechnology Institute Thurgau, University of Konstanz, Tägerwilen, Switzerland
6 Department of Internal Medicine, Division of Haematology and Oncology, Innsbruck Medical University, Austria
7 Biochemical Pharmacology, Faculty of Biology, University of Konstanz, Germany
8 Pulmonary Division, Department of Internal Medicine, University Hospital of Homburg, University of Saarland, D-66421 Homburg, Germany
Respiratory Research 2007, 8:50 doi:10.1186/1465-9921-8-50Published: 9 July 2007
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.
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 (106 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.
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.
Transplanted EPC may play an important role in reestablishing the endothelial integrity in vessels after severe injury or at inflamatory sites and might further contribute to vascular repair or wound healing processes in severely damaged tissue. Therapeutic applications of EPC transplantation may ensue.