Targeting CD93 in Infantile Hemangioma: Underlying Mechanisms of Angiogenesis and Therapeutic Intervention

<title>Abstract</title> <p> Objective To investigate the expression characteristics of CD93 in infantile hemangioma (IH) tissues, cells, and <italic>in vivo</italic> models, and to evaluate its biological function in IH angiogenesis as well as its potential value as a therapeutic target for anti-angiogenic therapy. Methods Clinical specimens from the proliferative and involuting phases of IH were collected. The expression levels of CD93 were detected using immunohistochemistry (IHC), immunofluorescence (IF), Western blotting (WB), and quantitative real-time PCR (qPCR). CD133 ⁺ hemangioma-derived stem cells (HemSCs) were isolated via collagenase digestion and CD133 immunomagnetic bead sorting. Stable cell lines with CD93 overexpression (CD93-OE) and knockdown (CD93-sh) were established using lentiviral transfection technology. The effects of CD93 and its polyclonal antibody on angiogenesis were assessed through <italic>in vitro</italic> tube formation assays. A subcutaneous xenograft model in BALB/c nude mice was constructed, and microvessel density (MVD) counting was performed to evaluate the regulatory role of CD93 in angiogenesis <italic>in vivo</italic> . Results CD93 was highly expressed in both proliferative-phase IH tissues and CD133 + HemSCs. <italic>In vitro</italic> experiments demonstrated that CD93 overexpression significantly enhanced the tube-forming ability of HemSCs, evidenced by increased total length, number of junctions, and number of meshes ( <italic>P</italic>  &lt; 0.05). Conversely, silencing CD93 or blocking with a CD93 polyclonal antibody significantly suppressed this function ( <italic>P</italic>  &lt; 0.05). The animal experiments successfully established a nude mouse model simulating IH proliferation and involution. <italic>In vivo</italic> angiogenesis results showed that the microvessel density (MVD) in the CD93 overexpression group was significantly higher than that in the control group (113.00 ± 16.95 vs. 67.67 ± 17.11 vessels/mm², <italic>P</italic>  &lt; 0.001), whereas the MVD in the CD93 knockdown and antibody blocking groups was significantly reduced ( <italic>P</italic>  &lt; 0.05). Conclusion CD93 is highly expressed during the proliferative phase of IH and significantly promotes the <italic>in vitro</italic> and <italic>in vivo</italic> angiogenic capacity of HemSCs. Targeted blockade of CD93 effectively inhibits angiogenesis, suggesting that CD93 is a promising novel therapeutic target for the treatment of IH. </p>