Hemangioma stem cells (HemSCs) are multipotent cells isolated from infantile hemangioma (IH), which form hemangioma-like lesions when injected subcutaneously into immune-deficient mice. In this murine model, HemSCs are the primary target of corticosteroid, a mainstay therapy for problematic IH. The relationship between HemSCs and endothelial cells that reside in IH is not clearly understood. Adhesive interactions might be critical for the preferential accumulation of HemSCs and/or endothelial cells in the tumor. Therefore, we studied the interactions between HemSCs and endothelial cells (HemECs) isolated from IH surgical specimens. We found that HemECs isolated from proliferating phase IH, but not involuting phase, constitutively express E-selectin, a cell adhesion molecule not present in quiescent endothelial cells. E-selectin was further increased when HemECs were exposed to vascular endothelial growth factor-A or tumor necrosis factor-α. In vitro, HemSC migration and adhesion was enhanced by recombinant E-selectin but not P-selectin; both processes were neutralized by E-selectin-blocking antibodies. E-selectin-positive HemECs also stimulated migration and adhesion of HemSCs. In vivo, neutralizing antibodies to E-selectin strongly inhibited formation of blood vessels when HemSCs and HemECs were co-implanted in Matrigel. These data suggest that endothelial E-selectin could be a major ligand for HemSCs and thereby promote cellular interactions and vasculogenesis in IH. We propose that constitutively expressed E-selectin on endothelial cells in the proliferating phase is one mediator of the stem cell tropism in IH.
Abstract Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone encoded by the SERPINH1 gene, has emerged as a groundbreaking focus in thrombosis research. Recent findings published in “Science” have revolutionized our understanding of thrombosis, identifying HSP47 as a critical mediator in a new thrombosis target for treatment. This discovery not only unveils a novel pathway in thrombosis but also opens new avenues for therapeutic intervention. HSP47's significance extends beyond thrombosis, influencing pathological processes such as fibrosis and cancer. In fibrosis, its upregulation promotes collagen deposition, while its dysregulation in osteogenesis imperfecta (OI) Type X underscores the protein's indispensable role in collagen biosynthesis. The therapeutic challenge lies in balancing HSP47 inhibition to reduce fibrotic burden without impairing its essential physiological functions. In cancer, HSP47 plays dual roles. It supports tumor progression through collagen stabilization and metastasis facilitation while contributing to tissue repair under hyperthermia treatment combined with radiotherapy or chemotherapy. However, its overexpression can exacerbate tumor aggressiveness via mechanisms such as angiogenesis and epithelial–mesenchymal transition. This review emphasizes the pivotal discovery of HSP47's thrombogenic role and its broader implications in disease biology. These findings mark a paradigm shift in thrombosis research and underscore the potential of HSP47 as a target in diverse pathological contexts, from platelet-driven diseases to fibrotic and oncological disorders.
<titre>Résumé</titre> La notion d’exception juridique est habituellement associée à des situations extrêmes de violence politique. Il est cependant possible de la penser comme un simple moment logique, constitutif du droit comme ordre discursif, et en même temps extérieur à lui. L’exception surgit ainsi dans le fonctionnement quotidien du droit, sous la forme d’un point aveugle que la logique du discours juridique ne parvient jamais à réduire. Cette contribution tente d’analyser ce désarroi du système juridique à travers deux cas dans lesquels il se dévoile : la rétention administrative des étrangers, et le débat contemporain en matière de bio-technologies. Elle cherche pour finir à tirer quelques conclusions sur la recomposition de la pensée juridique et politique face à ces cas limites.
This study aimed to assess platelet activation following implantation of the Aeson bioprosthetic total artificial heart (A-TAH). We monitored plasma levels of platelet activation markers in patients receiving A-TAH support (n = 16) throughout the follow-up period. Before implantation, soluble CD40 ligand (sCD40L) levels averaged 3,909.06 pg/ml (standard deviation [SD] = 3,772.37), remaining stable postimplantation at 3,964.56 pg/ml (SD = 2,198.85) during months 1–3 and at 3,519.27 pg/ml (SD = 1,647.04) during months 3–6. Similarly, P-selectin (sP-sel) levels were 35,235.36 pg/ml (SD = 14,940.47) before implantation, stabilizing to 33,158.96 pg/ml (SD = 9,023.11) (1–3 months) and 31,022.58 pg/ml (SD = 9,249.95) (3–6 months). Preimplantation platelet factor 4 (PF4) measured 2,593.47 ng/ml (SD = 2,167.85), remaining consistent at 2,136.10 ng/ml (SD = 1,264.47) (1–3 months) and 1,991.26 ng/ml (SD = 1,234.16) (3–6 months). Levels of neutrophil-activating peptide 2 (NAP2) were also steady, measuring 785.63 ng/ml (SD = 605.26) preimplantation, 935.10 ng/ml (SD = 517.73) at 1–3 months, and 907.21 ng/ml (SD = 501.96) at 3–6 months postimplantation. Importantly, neither aspirin nor heparin treatment affected these platelet biomarker levels. No correlation was observed between platelet activation marker levels and clinical outcomes such as pericardial effusion, nor with the timing of aspirin initiation and drain removal. Our findings confirm that A-TAH does not trigger platelet activation. The lack of association between aspirin, platelet activation, and clinical outcomes suggests the possibility of discontinuing antiplatelet therapy following A-TAH implantation in the future.
