Abstract
BackgroundBone 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.MethodsEx 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.ResultsWe 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.ConclusionTransplanted 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.
Highlights
Bone marrow-derived progenitors for both epithelial and endothelial cells have been observed in the lung
Recently published data suggest that repair mechanisms may in part rely on bone marrow-derived progenitor cells that are capable of differentiating in the directions that the injured site needs [3,12,13], and that there is a dose-relationship beween the degree of lung injury and the amount of repair cells stemming from the bone marrow [14]
Characteristics of ex vivo-generated bone marrow-derived rat endothelial progenitor cells (EPC) Cells were harvested from the non-adherent fraction of rat bone marrow mononuclear cells after 48 h of culture on fibronectin-coated culture dishes (Figure 1A)
Summary
Bone marrow-derived progenitors for both epithelial and endothelial cells have been observed in the lung. Severe tissue injury in ALI/ARDS is suggested to result further in an acute inflammatory response followed by repair processes that may result in additional apoptosis/necrosis of EC or epithelial cells [3,8,9,10]. The replacement of these dead cells during this repair process was formerly uniquely believed to be derived from cells in the vicinity of the damage within a given tissue [11]. Recently published data suggest that repair mechanisms may in part rely on bone marrow-derived progenitor cells that are capable of differentiating in the directions that the injured site needs [3,12,13], and that there is a dose-relationship beween the degree of lung injury and the amount of repair cells stemming from the bone marrow [14]
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