Circulating endothelial progenitor cells as a pathogenetic marker of moyamoya disease
Keun-Hwa Jung1, Kon Chu, Soon-Tae Lee
1Stroke and Stem Cell Laboratory, Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Abstract:
Moyamoya disease (MMD) is an unusual form of chronic cerebrovascular occlusive disease that involves the formation of characteristically abnormal vessels. Recent studies have reported that colony-forming unit (CFU) and outgrowth cells represent a subpopulation of endothelial progenitor cells (EPCs). Here, we attempted to determine the significance of CFU number and outgrowth cell yield in MMD. Endothelial progenitor cells were isolated from the blood of 24 adult MMD patients and from 48 age- and risk factor-matched control subjects. After 7 days of culture, CFUs were determined, and yields of outgrowth cells were measured during 2 months of culture. The EPC function was also evaluated using matrigel plate assays. It was found that CFU numbers were significantly lower in MMD patients than in controls. Moreover, during long-term culture, outgrowth cells were isolated from only 10% of control subjects but from 33% of MMD patients, and CFU numbers and tube formation were found to be lower in advanced MMD cases than in those with early stage disease, whereas outgrowth cells were more frequently detected in those with early MMD and moyamoya vessels than in those with advanced disease. These characteristics of circulating EPCs reflect mixed conditions of vascular occlusion and abnormal vasculogenesis during the pathogenesis of MMD.
Insights
Endothelial progenitor cells (EPCs) are altered in Moyamoya disease (MMD). Lower colony-forming units (CFUs) and altered outgrowth cells in MMD patients suggest impaired vascular repair mechanisms in this cerebrovascular condition.
Area of Science:
- Cardiovascular Research
- Neuroscience
- Cell Biology
Background:
- Moyamoya disease (MMD) is a rare cerebrovascular occlusive disorder characterized by abnormal vessel formation.
- Endothelial progenitor cells (EPCs), including colony-forming units (CFUs) and outgrowth cells, are crucial for vascular repair.
- The role of EPC subpopulations in MMD pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the significance of CFU number and outgrowth cell yield in adult Moyamoya disease patients.
- To compare EPC characteristics between MMD patients and matched healthy controls.
- To evaluate the correlation between EPC function and MMD disease stage.
Main Methods:
- Isolation of EPCs from peripheral blood of 24 adult MMD patients and 48 controls.
- Culture of EPCs for 7 days to determine CFU counts and for 2 months to measure outgrowth cell yields.
- Assessment of EPC function using matrigel assays and evaluation of tube formation.
Main Results:
- Significantly lower CFU numbers were observed in MMD patients compared to controls.
- Outgrowth cells were more frequently detected in MMD patients (33%) than in controls (10%).
- Advanced MMD cases showed reduced CFU numbers and tube formation, while early MMD stages were associated with more frequent outgrowth cell detection.
Conclusions:
- Circulating EPC characteristics, including reduced CFUs and altered outgrowth cell dynamics, are indicative of MMD.
- These findings suggest impaired vascular repair and abnormal vasculogenesis contribute to MMD pathogenesis.
- EPC analysis may offer insights into the complex vascular conditions present in Moyamoya disease.
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