CD90 Identifies Adventitial Mesenchymal Progenitor Cells in Adult Human Medium- and Large-Sized Arteries

• Published in: Stem cell reports Vol. 11; no. 1; pp. 242 - 257
• Main Authors: Michelis, Katherine C., Nomura-Kitabayashi, Aya, Lecce, Laura, Franzén, Oscar, Koplev, Simon, Xu, Yang, Santini, Maria Paola, D'Escamard, Valentina, Lee, Jonathan T.L., Fuster, Valentin, Hajjar, Roger, Reddy, Ramachandra C., Chikwe, Joanna, Stelzer, Paul, Filsoufi, Farzan, Stewart, Allan, Anyanwu, Anelechi, Björkegren, Johan L.M., Kovacic, Jason C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.07.2018; Elsevier
• Subjects: adventitia; Arteries - embryology; Arteries - metabolism; atherosclersis; Biomarkers; cardiovascular; Cell Differentiation - genetics; Gene Expression Profiling; Humans; Immunophenotyping; Ischemia - etiology; Ischemia - metabolism; Medicin och hälsovetenskap; mesenchymal stem cell; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Neovascularization, Physiologic - genetics; Thy-1 Antigens - genetics; Thy-1 Antigens - metabolism; mesenchymal stem cell; adventitia; cardiovascular; atherosclersis
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2018.06.001

Mesenchymal stem cells (MSCs) reportedly exist in a vascular niche occupying the outer adventitial layer. However, these cells have not been well characterized in vivo in medium- and large-sized arteries in humans, and their potential pathological role is unknown. To address this, healthy and diseased arterial tissues were obtained as surplus surgical specimens and freshly processed. We identified that CD90 marks a rare adventitial population that co-expresses MSC markers including PDGFRα, CD44, CD73, and CD105. However, unlike CD90, these additional markers were widely expressed by other cells. Human adventitial CD90+ cells fulfilled standard MSC criteria, including plastic adherence, spindle morphology, passage ability, colony formation, and differentiation into adipocytes, osteoblasts, and chondrocytes. Phenotypic and transcriptomic profiling, as well as adoptive transfer experiments, revealed a potential role in vascular disease pathogenesis, with the transcriptomic disease signature of these cells being represented in an aortic regulatory gene network that is operative in atherosclerosis. •We identify, in situ and in vivo, adventitial CD90+ MSCs in human arteries•Human adventitial CD90+ cells fulfill all criteria for an MSC population•Other markers, such as CD44 and PDGFRα, were non-specific for adventitial MSCs•The CD90+ MSC transcriptomic signature suggests a major role in vascular disease MSCs reportedly exist in a specific vascular niche, but these cells have not been well characterized in medium- and large-sized human arteries. To address this, surplus arterial tissues were obtained at surgery and freshly processed. We show that CD90 marks a human adventitial MSC population, with the CD90+ MSC transcriptomic signature being represented in an atherosclerotic regulatory gene network.