The crosstalk between vascular MSCs and inflammatory mediators determines the pro-calcific remodelling of human atherosclerotic aneurysm

• Published in: Stem cell research & therapy 2017-04, Vol.8 (1), p.99-99, Article 99
• Main Authors: Ciavarella, Carmen, Gallitto, Enrico, Ricci, Francesca, Buzzi, Marina, Stella, Andrea, Pasquinelli, Gianandrea
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Abdomen; Adipocytes; Adipose tissue; AKT protein; Aneurysms; Angiogenesis; Animal models; Antigens; Aorta; Aorta - metabolism; Aorta - pathology; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - pathology; Aortic aneurysms; Arteries; Arteriosclerosis; Atherosclerosis; Atherosclerotic aneurysm; Autocrine signalling; Biomarkers - metabolism; Biotin; Bone marrow; Calcification; Calcium - metabolism; CD146 Antigen - metabolism; Cell Communication; Cell Differentiation; Cell Lineage; Cells, Cultured; Clotting; Coronary vessels; Cytokines; Gene expression; Glycoproteins - metabolism; Human aortic mesenchymal stem cells; Humans; Hypoxia; IL-1β; Immunogenicity; Immunosuppression; Inflammation; Inflammation Mediators - metabolism; Interleukin-10 - metabolism; Interleukin-1beta - metabolism; Leukocytes, Mononuclear - metabolism; Matrix Metalloproteinase 9 - blood; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Nodules; Osteogenesis; Pathogenesis; PPAR gamma - metabolism; Smooth muscle; Stem cells; Studies; Surgery; Temperature effects; Tumor Necrosis Factor-alpha - metabolism; Vascular Remodeling; Vascular remodelling
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-017-0554-x

Human mesenchymal stem cells (MSCs) possess well-known reparative abilities, but any defect of the immunomodulatory activity and/or the differentiation process may determine the development of human diseases, including those affecting the vascular wall. MSCs residing within the human aortic wall represent a potential cell mediator of atherosclerotic aneurysm development. MSCs isolated from healthy and aneurysm aortas were characterized by flow cytometer and tested for differentiation properties. Healthy aorta (ha)-MSCs were then subjected to inflammatory stimuli to evaluate the microenvironmental impact on their function and involvement in vascular remodelling. Abdominal aortic aneurysm (AAA)-MSCs were isolated from calcified and inflamed aortas of 12 patients with high serum levels of MMP-9 protein. AAA-MSCs expressed typical mesenchymal markers and, in line with the histological analysis, elevated levels of OPN, an osteogenic marker also involved in vascular remodelling. AAA-MSCs were highly osteogenic and underwent intense calcium deposition under proper stimulation; moreover, AAA-MSCs were able to differentiate into tubule-like structures in Matrigel, even if the lack of CD146 and the reduced structural stability suggested an inefficient maturation process. We further demonstrated an association between osteogenesis and inflammation; indeed, ha-MSCs cultured with either cytokines (TNF-α, IL-1β) or AAA-PBMCs showed increased expression of MMP-9 and osteogenic markers, to the detriment of the adipogenic regulator PPAR-γ. Interestingly, the culture with inflammatory cells highly stimulated ha-MSCs towards the osteogenic commitment. AAA-MSCs displayed high osteogenic potential and pathological angiogenesis that represent crucial steps for AAA progression; we showed that the inflammatory process critically addresses human vascular MSCs towards a pathological behaviour, inducing vascular bone matrix deposition and remodelling. Inhibition of this pathway may represent a pharmacological approach against arterial calcification.