Abstract 527: Transplantation of Mesenchymal Stem Cells Improves Endothelial Function of Lungs in Monocrotaline-Induced Pulmonary Hypertensive Rats
Background: Mesenchymal stem cells (MSCs) are known to accumulate in various cardiovascular lesions. We assessed the distribution of transplanted MSCs and the effect of MSC-transplantation on the endothelial function in the monocrotaline-induced pulmonary hypertension (PH) in rats.
Methods: MSCs were obtained by culturing bone marrow mononuclear cells of Lewis rats. In Lewis rats, PH was induced by injecting monocrotaline at 7 weeks old. To assess the distribution of MSCs after transplantation, 111Indium oxine-labeled MSCs or GFP-gene transfected MSCs (5 × 10^5 cells/rat) were transplanted intravenously 2 weeks after monocrotaline treatment (n=5/group). The radioactivities in the lung, liver, and other organs were measured 1 and 14 days after MSCs transplantation. The distribution of GFP-positive cells in the lungs was observed by a fluorescent microscope. To assess the effect of MSC-transplantation on endothelial function, the 5 × 10^5 of MSCs were transplanted intravenously 2 weeks after the injection of monocrotaline and eNOS in the lungs was evaluated at 14 days after MSC-transplantation.
Results: In the non-PH rats, the lung contained 2.6+/-0.3% and 0.7+/-0.3% of transplanted MSCs at 1 and 14 days after transplantation, respectively. In PH rats, the number of accumulated MSCs in the lung increased by 8.5+/-2.5% and 4.0+/-1.1% at 1 and 14 days, respectively. Monocrotaline did not affect MSCs accumulation in other organs. The GFP positive transplanted cells were found in the perivascular space but few in the vascular lumen in the lungs. In PH rats, eNOS expression decreased to 60.6+/-27.6% of that in non-PH rats. MSC transplantation reversed the eNOS expression levels of PH rats to 75.6+/-24.8% of that in non-PH rats.
Conclusions: MSCs preferentially accumulated in the lungs of PH rats. It was suggested that they contributed to ameliorate the endothelial dysfunction in PH rats.