TY - JOUR
T1 - CD90 Identifies Adventitial Mesenchymal Progenitor Cells in Adult Human Medium- and Large-Sized Arteries
AU - Michelis, Katherine C.
AU - Nomura-Kitabayashi, Aya
AU - Lecce, Laura
AU - Franzén, Oscar
AU - Koplev, Simon
AU - Xu, Yang
AU - Santini, Maria Paola
AU - D'Escamard, Valentina
AU - Lee, Jonathan T.L.
AU - Fuster, Valentin
AU - Hajjar, Roger
AU - Reddy, Ramachandra C.
AU - Chikwe, Joanna
AU - Stelzer, Paul
AU - Filsoufi, Farzan
AU - Stewart, Allan
AU - Anyanwu, Anelechi
AU - Björkegren, Johan L.M.
AU - Kovacic, Jason C.
N1 - Funding Information:
We thank the Fondation Leducq (Transatlantic Network of Excellence Awards) for funding the analyses described herein. K.C.M., A.N.-K., and V.D. were supported by the NIH (T32HL007824). J.C.K. also acknowledges research support from the NIH (R01HL130423) and the American Heart Association (14SFRN20490315 and 14SFRN20840000). J.L.M.B. acknowledges research support from AstraZeneca, the NIH (R01HL125863), and Fondation Leducq. We acknowledge the assistance and technical expertise of the Genomics and Multiscale Biology, Histopathology and Flow Cytometry Core Facilities at the Icahn School of Medicine at Mount Sinai.
Funding Information:
We thank the Fondation Leducq (Transatlantic Network of Excellence Awards) for funding the analyses described herein. K.C.M., A.N.-K., and V.D. were supported by the NIH ( T32HL007824 ). J.C.K. also acknowledges research support from the NIH ( R01HL130423 ) and the American Heart Association ( 14SFRN20490315 and 14SFRN20840000 ). J.L.M.B. acknowledges research support from AstraZeneca , the NIH ( R01HL125863 ), and Fondation Leducq . We acknowledge the assistance and technical expertise of the Genomics and Multiscale Biology, Histopathology and Flow Cytometry Core Facilities at the Icahn School of Medicine at Mount Sinai.
Publisher Copyright:
© 2018 The Authors
PY - 2018/7/10
Y1 - 2018/7/10
N2 - 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. 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.
AB - 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. 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.
KW - adventitia
KW - atherosclersis
KW - cardiovascular
KW - mesenchymal stem cell
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U2 - 10.1016/j.stemcr.2018.06.001
DO - 10.1016/j.stemcr.2018.06.001
M3 - Article
C2 - 30008326
AN - SCOPUS:85049012683
SN - 2213-6711
VL - 11
SP - 242
EP - 257
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -