Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension

Amy L. Firth, Weijuan Yao, Aiko Ogawa, Michael M. Madani, Grace Y. Lin, Jason Yuan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Factors contributing to the development of a fibrotic vascular scar and pulmonary vascular remodeling leading to chronic thromboembolic pulmonary hypertension (CTEPH) are still unknown. This study investigates the potential contribution of multipotent progenitor cells and myofibroblasts to the development and progression of CTEPH. Histological examination of endarterectomized tissues from patients with CTEPH identified significant neointimal formation. Morphological heterogeneity was observed in cells isolated from these tissues, including a network-like growth pattern and the formation of colonyforming unit-fibroblast-like colonies (CFU-F). Cells typically coexpressed intermediate filaments vimentin and smooth muscle α-actin. Cells were characterized by immunofluorescence and quantitated by fluorescent-activated cell sorting (FACS) for the presence of cell surface markers typical of mesenchymal progenitor cells; cells were >99% CD44 + CD73+, CD90+, CD166+; >80% CD29+; 45-99% CD105+; CD34- and CD45 -. Cells were capable of adipogenic and osteogenic differentiation, determined by Oil Red O and Alizarin Red staining, respectively. Additionally, a population of Stro-1+ cells, a marker of bone marrow-derived stromal cells (4.2%), was sorted by FACS and also capable of adipogenic and osteogenic differentiation. In conclusion, this study is the first to identify a myofibroblast cell phenotype to be predominant within endarterectomized tissues, contributing extensively to the vascular lesion/clot. This cell may arise from transdifferentiation of adventitial fibroblasts or differentiation of mesenchymal progenitor cells. The unique microenvironment created by the stabilized clot is likely a factor in stimulating such cellular changes. These findings will be critical in establishing future studies in the development of novel and much needed therapeutic approaches for pulmonary hypertension.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume298
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Pulmonary Hypertension
Myofibroblasts
Blood Vessels
Fibroblasts
Adventitia
Intermediate Filaments
Vimentin
Cicatrix
Fluorescent Antibody Technique
Smooth Muscle
Actins
Stem Cells
Staining and Labeling
Phenotype
Lung

Keywords

  • Chronic thromboembolic pulmonary hypertension
  • Occlusion
  • Progenitor cells
  • Remodeling

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension. / Firth, Amy L.; Yao, Weijuan; Ogawa, Aiko; Madani, Michael M.; Lin, Grace Y.; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 298, No. 5, 05.2010.

Research output: Contribution to journalArticle

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abstract = "Factors contributing to the development of a fibrotic vascular scar and pulmonary vascular remodeling leading to chronic thromboembolic pulmonary hypertension (CTEPH) are still unknown. This study investigates the potential contribution of multipotent progenitor cells and myofibroblasts to the development and progression of CTEPH. Histological examination of endarterectomized tissues from patients with CTEPH identified significant neointimal formation. Morphological heterogeneity was observed in cells isolated from these tissues, including a network-like growth pattern and the formation of colonyforming unit-fibroblast-like colonies (CFU-F). Cells typically coexpressed intermediate filaments vimentin and smooth muscle α-actin. Cells were characterized by immunofluorescence and quantitated by fluorescent-activated cell sorting (FACS) for the presence of cell surface markers typical of mesenchymal progenitor cells; cells were >99{\%} CD44 + CD73+, CD90+, CD166+; >80{\%} CD29+; 45-99{\%} CD105+; CD34- and CD45 -. Cells were capable of adipogenic and osteogenic differentiation, determined by Oil Red O and Alizarin Red staining, respectively. Additionally, a population of Stro-1+ cells, a marker of bone marrow-derived stromal cells (4.2{\%}), was sorted by FACS and also capable of adipogenic and osteogenic differentiation. In conclusion, this study is the first to identify a myofibroblast cell phenotype to be predominant within endarterectomized tissues, contributing extensively to the vascular lesion/clot. This cell may arise from transdifferentiation of adventitial fibroblasts or differentiation of mesenchymal progenitor cells. The unique microenvironment created by the stabilized clot is likely a factor in stimulating such cellular changes. These findings will be critical in establishing future studies in the development of novel and much needed therapeutic approaches for pulmonary hypertension.",
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