摘要
Background Infantile hemangioma （IH） is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration. Methods Stem cells from the proliferating hemangiomas （HemSCs） were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction （PCR）, immunofluorescent staining and injection into BALB/c-nu mice. Results HemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell （MSC）. Real-time PCR showed that the mRNA levels of vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF） and matrix metalloproteinase-1 （MMP-1） of HemSCs were higher than that of neonatal human dermal fibroblasts （NHDFs） and human umbilical vein endothelial cells （HUVECs）. After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time （16 hours） and differentiated into endothelial cells in 7 days. After 1-2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice （P 〈0.05）. Conclusions HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.
Background Infantile hemangioma （IH） is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration. Methods Stem cells from the proliferating hemangiomas （HemSCs） were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction （PCR）, immunofluorescent staining and injection into BALB/c-nu mice. Results HemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell （MSC）. Real-time PCR showed that the mRNA levels of vascular endothelial growth factor （VEGF）, basic fibroblast growth factor （bFGF） and matrix metalloproteinase-1 （MMP-1） of HemSCs were higher than that of neonatal human dermal fibroblasts （NHDFs） and human umbilical vein endothelial cells （HUVECs）. After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time （16 hours） and differentiated into endothelial cells in 7 days. After 1-2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice （P 〈0.05）. Conclusions HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.
基金
This work was supported by grants from the National Natural Science Foundation of China （No. 81070846）, Shanghai Leading Academic Discipline Project （No. S30206）.
