Arterial calcification: Finger-pointing at resident and circulating stem cells

Abstract

The term ‘‘Stammzelle’’ (stem cells) originally appeared in 1868 in the works of Ernst Haeckel who used it to describe the ancestor unicellular organism from which he presumed all multicellular organisms evolved. Since then stem cells have been studied in a wide spectrum of normal and pathological conditions; it is remarkable to note that ectopic arterial calcification was considered a passive deposit of calcium since its original discovering in 1877; in the last decades, resident and circulating stem cells were imaged to drive arterial calcification through chondro-osteogenic differentiation thus opening the idea that an active mechanism could be at the basis of the process that clinically shows a Janus effect: calcifications either lead to the stabilization or rupture of the atherosclerotic plaques. A review of the literature underlines that 130 years after stem cell discovery, antigenic markers of stem cells are still debated and the identification of the osteoprogenitor phenotype is even more elusive due to tissue degradation occurring at processing and manipulation. It is necessary to find a consensus to perform comparable studies that implies phenotypic recognition of stem cells antigens. A hypothesis is based on the singular morphology and amitotic mechanism of division of osteoclasts: it constitutes the opening to a new approach on osteoprogenitors markers and recognition. Our aim was to highlight all the present evidences of the active calcification process, summarize the different cellular types involved, and discuss a novel approach to discover osteoprogenitor phenotypes in arterial wall.

Keywords: Osteocalcin, Osteoprogenitor, Stem cells markers, Arterial calcification, Resident and circulating

Core tip: We review state of art on active arterial calcification, introduce new insight in arterial osteoprogenitors (OPs) phenotypes and the concept of amitosis. Analysis of literature of all markers used to define mesenchymal stem cells and OPs revealed the evident incongruity between the actual studies: each research has its own panel of antigen markers. Still, osteocalcin resulted the most promising marker of resident and circulating OPs. A new technique allows maintaining DNA/RNA integrity in highly calcified or ectopic bone formation: new studies should consider this technique and the particular division of OPs to identify them.