Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension.
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
Jeffrey L
JL
Department of Medicine, Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Whitney
Mandolin J
MJ
Sullivan
Deborah E
DE
Lasky
Joseph A
JA
Laboy
Miguel
M
Ylostalo
Joni
J
Prockop
Darwin J
DJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014945:Wound Healing
D049452:Green Fluorescent Proteins; D016686:Monocrotaline