Background: Sirolimus, a mammalian target of rapamycin inhibitor, has been widely used in pediatric patients, but the safety of sirolimus in pediatric patients has not been well determined. Objective: The objective of this study was to systematically evaluate prospective studies reporting the safety of sirolimus in the treatment of childhood diseases. Methods: The following data were extracted in a standardized manner: study design, demographic characteristics, intervention, and safety outcomes. Results: In total, 9 studies were included, encompassing 575 patients who received oral sirolimus for at least 6 months. Various adverse events occurred. The most common adverse event was oral mucositis (8.2%, 95% CI: 0.054 to 0.110). Through comparative analysis of the subgroups based on the targeted concentration range, we discovered that many adverse events were significantly higher in the high concentration group (≥10 ng/mL) than in the low concentration group (<10 ng/mL) (p < 0.01). More interestingly, we found that oral mucositis was more frequently reported in children with vascular anomalies than tuberous sclerosis complex. Conclusions: This study shows that oral sirolimus in the treatment of childhood diseases is safe and reliable. However, sirolimus treatment in the pediatric population should be strictly monitored to reduce the occurrence of serious or fatal adverse events.

Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

Infantile hemangioma (IH) is the most prevalent type of vascular tumor in infants. The pathophysiology of IH is unknown. The tissue structure and physiology of two-dimensional cell cultures differ greatly from those in vivo, and spontaneous regression often occurs during tumor formation in nude mice and has severely limited research into the pathogenesis and development of IH. By decellularizing porcine aorta, we attempted to obtain vascular-specific extracellular matrix as the bioink for fabricating micropattern arrays of varying diameters via microcontact printing. We then constructed IH-derived CD31+ hemangioma endothelial cell three-dimensional microtumor models. The vascular-specific and decellularized extracellular matrix was suitable for the growth of infantile hemangioma-derived endothelial cells. The KEGG signaling pathway analysis revealed enrichment primarily in stem cell pluripotency, RAS, and PI3KAkt compared to the two-dimensional cell model according to RNA sequencing. Propranolol, the first-line medication for IH, was also used to test the model’s applicability. We also found that metformin had some impact on the condition. The three-dimensional microtumor models of CD31+ hemangioma endothelial cells were more robust and efficient experimental models for IH mechanistic exploration and drug screening.