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Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension

Jeffrey L. Spees^*,,1, Mandolin J. Whitney^*, Deborah E. Sullivan, Joseph A. Lasky, Miguel Laboy, Joni Ylostalo^* and Darwin J. Prockop^*

^* Department of Medicine, Center for Gene Therapy and

Section of Pulmonary Diseases, Critical Care, and Environmental Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana, USA; and

Department of Medicine, Cardiovascular Research Institute, University of Vermont, Colchester, Vermont, USA

¹Correspondence: Department of Medicine, Cardiovascular Research Institute, University of Vermont, 208 South Park Dr., Ste. 2, Colchester, VT 05446, USA. E-mail: jeffrey.spees{at}uvm.edu

Infusion of bone marrow stem or progenitor cells may provide powerful therapies for injured tissues such as the lung and heart. We examined the potential of bone marrow-derived (BMD) progenitor cells to contribute to repair and remodeling of lung and heart in a rat monocrotaline (MCT) model of pulmonary hypertension. Bone marrow from green fluorescent protein (GFP)-transgenic male rats was transplanted into GFP-negative female rats. The chimeric animals were injected with MCT to produce pulmonary hypertension. Significant numbers of male GFP-positive BMD cells engrafted in the lungs of MCT-treated rats. Microarray analyses and double-immunohistochemistry demonstrated that many of the cells were interstitial fibroblasts or myofibroblasts, some of the cells were hematopoietic cells, and some were pulmonary epithelial cells (Clara cells), vascular endothelial cells, and smooth muscle cells. A few BMD cells fused with pulmonary cells from the host, but the frequency was low. In the hypertrophied hearts of MCT-treated rats, we found a significant increase in the relative numbers of BMD cells in the right ventricle wall as compared with the left ventricle. Some of the BMD cells in the right ventricle were vascular cells and cardiomyocytes. We report BMD cardiomyocytes with a normal chromosome number, fusion of BMD cells with host cardiomyocytes, and, in some cases, nuclear fusion.—Spees, J. L., Whitney, M. J., Sullivan, D. E., Lasky, J. A., Laboy, M., Ylostalo, J., Prockop, D. J. Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension.

Key Words: stem cell • monocrotaline • cardiac hypertrophy

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