title: CD34-negative mesenchymal stem-like cells may act as the cellular origin of human aortic valve calcification.
abstract: Although various osteogenic inducers contribute to the calcification of human aortic valve interstitial cells, the cellular origin of calcification remains unclear. We immunohistochemically investigated the cellular origin of valve calcification using enzymatically isolated cells from both calcified and non-calcified human aortic valve specimens. CD73-, 90-, and 105-positive and CD45-negative mesenchymal stem-like cells (MSLCs) were isolated from both types of valve specimens using fluorescence-activated cell sorting. MSLCs were further sorted into CD34-negative and -positive cells. Compared with CD34-positive cells, CD34-negative MSLCs were significantly more sensitive to high inorganic phosphate (3.2 mM), calcifying easily in response. Furthermore, immunohistochemical staining showed that significantly higher numbers (~7-9-fold) of CD34-negative compared with CD34-positive MSLCs were localized in calcified aortic valve specimens obtained from calcified aortic stenosis patients. These results suggest that CD34-negative MSLCs are responsible for calcification of the aortic valve.
authors.affiliation: Department of Pharmacology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan; Department of Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Anan
authors.initials: A
authors.lastname: Nomura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Seya
authors.forename: Zaiqiang
authors.initials: Z
authors.lastname: Yu
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Daitoku
authors.forename: Shigeru
authors.initials: S
authors.lastname: Motomura
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Ikuo
authors.initials: I
authors.lastname: Fukuda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D001021:Aortic Valve / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000139:chemically induced / Q000473:pathology*; D002114:Calcinosis / Q000139:chemically induced / Q000473:pathology*; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D010710:Phosphates
keywords: Aortic valve; CD34; Calcific aortic stenosis; Calcification; Inorganic phosphate; Mesenchymal stem-like cell