Smooth-muscle progenitor cells isolated from patients with moyamoya disease: novel experimental cell model
Laboratory investigation
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Translational Genomics Laboratory, Samsung Genome Institute, Samsung Medical Center, Seoul; and
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul;
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Object
Moyamoya disease (MMD) is a cerebrovascular occlusive disease affecting bilateral internal carotid termini. Smooth-muscle cells are one of the major cell types involved in this disease process. The characteristics of circulating smooth-muscle progenitor cells (SPCs) in MMD are poorly understood. The authors purified SPCs from the peripheral blood of patients with MMD and sought to identify differentially expressed genes (DEGs) in SPCs from these patients.
Methods
The authors cultured and isolated SPCs from the peripheral blood of patients with MMD (n = 25) and healthy control volunteers (n = 22). After confirmation of the cellular phenotype, RNA was extracted from the cells and DEGs were identified using a commercially available gene chip. Real-time quantitative reverse transcription polymerase chain reaction was performed to confirm the putative pathogenetic DEGs.
Results
The SPC-type outgrowth cells in patients with MMD invariably showed a hill-and-valley appearance under microscopic examination, and demonstrated high α–smooth muscle actin, myosin heavy chain, and calponin expression (96.5% ± 2.1%, 42.8% ± 18.6%, and 87.1% ± 8.2%, respectively), and minimal CD31 expression (less than 1%) on fluorescence-activated cell sorter analysis. The SPCs in the MMD group tended to make more irregularly arranged and thickened tubules on the tube formation assay. In the SPCs from patients with MMD, 286 genes (124 upregulated and 162 downregulated) were differentially expressed; they were related to cell adhesion, cell migration, immune response, and vascular development.
Conclusions
With adequate culture conditions, SPCs could be established from the peripheral blood of patients with MMD. These cells showed specific DEGs compared with healthy control volunteers. This study provides a novel experimental cell model for further research of MMD.
Abbreviations used in this paper:
α-SMA = α–smooth muscle actin; DEG = differentially expressed gene; EPC = endothelial progenitor cell; FACS = fluorescence-activated cell sorter; FSP-1 = fibroblast-specific protein–1; GO = gene ontology; GTPase = guanosine 5′-triphosphatase; KEGG = Kyoto Encyclopedia of Genes and Genomes; MCAM = melanoma cell adhesion molecule; MHC = myosin heavy chain; MMD = moyamoya disease; PBS = phosphate-buffered saline; PDGF, PDGFR = platelet-derived growth factor, PDGF receptor; qRT-PCR = quantitative reverse transcription polymerase chain reaction; SMC = smooth-muscle cell; SPC = smooth-muscle progenitor cell; VEGF, VEGFR = vascular endothelial growth factor, VEGF receptor.
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