Itinteang Tinte, Tan Cherise E S, van Schaijik Bede, Marsh Reginald W, Davis Paul F, Tan Swee T
Gillies McIndoe Research Institute, Newtown, Wellington, New Zealand.
the Centre for the Study & Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Lower Hutt, New Zealand.
Plast Reconstr Surg Glob Open. 2020 Feb 11;8(2):e2598. doi: 10.1097/GOX.0000000000002598. eCollection 2020 Feb.
We have previously shown that the endothelium of the microvessels of infantile hemangioma (IH) exhibits a hemogenic endothelium phenotype and proposed its potential to give rise to mesenchymal stem cells, similar to the development of hematopoietic cells. This endothelial-to-mesenchymal transition (Endo-MT) process involves the acquisition of a migratory phenotype by the endothelial cells, similar to epithelial-to-mesenchymal transition that occurs during neural crest development. We hypothesized that proliferating IH expresses Endo-MT-associated proteins and investigated their expression at the mRNA, protein, and functional levels.
Immunohistochemical staining of paraffin-embedded sections of proliferating IH samples from 10 patients was undertaken to investigate the expression of the Endo-MT proteins Twist1, Twist2, Snail1, and Slug. Transcriptional analysis was performed for the same markers on proliferating IH tissues and CD34 and CD34 cells from proliferating IH-derived primary cell lines. Adipogenic and osteogenic differentiation plasticity was determined on the CD34-sorted fractions.
The endothelium of the microvessels and the cells within the interstitium of proliferating IH tissues expressed Twist1, Twist2, and Slug proteins. Twist1 was also expressed on the pericyte layer of the microvessels, whereas Snail1 was not expressed. Both CD34 and CD34 populations from the IH-derived primary cell lines underwent adipogenic and osteogenic differentiation.
The expression of Endo-MT-associated proteins Twist1, Twist2, and Slug by both the endothelium of the microvessels and cells within the interstitium, and Twist1 on the pericyte layer of the microvessels of proliferating IH, suggest the presence of a process similar to Endo-MT. This may enable a tightly controlled primitive endothelium of proliferating IH to acquire a migratory mesenchymal phenotype with the ability to migrate away, providing a plausible explanation for the development of a fibrofatty residuum observed during involution of IH.
我们之前已经表明，婴儿血管瘤（IH）微血管的内皮细胞表现出血源性内皮细胞表型，并提出其具有产生间充质干细胞的潜力，类似于造血细胞的发育过程。这种内皮 - 间充质转化（Endo - MT）过程涉及内皮细胞获得迁移表型，类似于神经嵴发育过程中发生的上皮 - 间充质转化。我们假设增殖期的IH表达Endo - MT相关蛋白，并在mRNA、蛋白质和功能水平上研究它们的表达。
对10例患者增殖期IH样本的石蜡包埋切片进行免疫组织化学染色，以研究Endo - MT蛋白Twist1、Twist2、Snail1和Slug的表达。对增殖期IH组织以及来自增殖期IH衍生的原代细胞系的CD34⁺和CD34⁻细胞进行相同标志物的转录分析。在CD34分选的组分上测定成脂和成骨分化可塑性。
增殖期IH组织的微血管内皮细胞和间质内的细胞表达Twist1、Twist2和Slug蛋白。Twist1也在微血管的周细胞层表达，而Snail1未表达。来自IH衍生原代细胞系的CD34⁺和CD34⁻群体均经历了成脂和成骨分化。
增殖期IH的微血管内皮细胞和间质内的细胞均表达Endo - MT相关蛋白Twist1、Twist2和Slug，且Twist1在增殖期IH微血管的周细胞层表达，提示存在类似于Endo - MT的过程。这可能使增殖期IH紧密受控的原始内皮细胞获得迁移的间充质表型并具有迁移离开的能力，为IH消退过程中观察到的纤维脂肪残留物的形成提供了合理的解释。
