scholarly journals Identification of putative endothelial progenitor cells (CD34+CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

2009 ◽  
Vol 296 (6) ◽  
pp. L870-L878 ◽  
Author(s):  
Weijuan Yao ◽  
Amy L. Firth ◽  
Richard S. Sacks ◽  
Aiko Ogawa ◽  
William R. Auger ◽  
...  

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)-positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34+Flk-1+CD133+cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

2010 ◽  
Vol 298 (5) ◽  
pp. C1217-C1225 ◽  
Author(s):  
Amy L. Firth ◽  
Weijuan Yao ◽  
Aiko Ogawa ◽  
Michael M. Madani ◽  
Grace Y. Lin ◽  
...  

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 colony-forming 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.


Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.


2007 ◽  
Vol 98 (11) ◽  
pp. 930-939 ◽  
Author(s):  
Derya Tilki ◽  
Hans-Peter Hohn ◽  
Ursula Gehling ◽  
Nerbil Kilic ◽  
Süleyman Ergün

SummaryA rapidly increasing body of data suggests an essential role of endothelial progenitor cells (EPCs) in vascular regeneration, formation of new vessels in cardiovascular diseases and also in tumor vasculogenesis. Moreover, recent data obtained from clinical studies with anti-angiogenic drugs in tumor therapy or with pro-angiogenic stimuli in ischemic disorders implicate a predictive role of the number of EPCs circulating in the peripheral blood in monitoring of these diseases. However, there is still some controversial data regarding the relevance of the EPCs in vascular formation depending on models used and diseases studied. One of the essential prerequisites for a better understanding of the whole contribution of EPCs to vascular formation in adult, a process called postnatal vasculogenesis, is to identify their exact sources. We could recently discover the existence of EPCs in a distinct zone of the vascular wall of large and middle sized adult blood vessels and showed that these cells are capable to differentiate into mature endothelial cells, to form capillary sprouts in arterial ring assay and to build vasa vasorumlike structures within the vascular wall. They also can be mobilized very rapidly from the vascular wall by tumor cells. This review will discuss the functional implications of these vascular wall resident endothelial progenitor cells (VW-EPCs) in relation to those of EPCs circulating in peripheral blood or derived from the bone marrow in cardiovascular and neoplastic diseases.


ASAIO Journal ◽  
2002 ◽  
Vol 48 (2) ◽  
pp. 188
Author(s):  
Mitsuru Takahashi ◽  
Tatsuo Nakamura ◽  
Toshinari Toba ◽  
Seijyun Fukuda ◽  
Makoto Yoshitani ◽  
...  

2004 ◽  
Vol 10 (5-6) ◽  
pp. 771-779 ◽  
Author(s):  
Mitsuru Takahashi ◽  
Tatsuo Nakamura ◽  
Toshinari Toba ◽  
Naohiro Kajiwara ◽  
Harubumi Kato ◽  
...  

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