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A histological study of vascular wall resident stem cells in venous malformations

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Abstract

Vascular wall resident stem cells (VW-SCs) play a key role in vascular formation and remodeling under both physiological and pathological situations. They not only serve as a reservoir to supply all types of vascular cells needed, but also regulate vascular homeostasis by paracrine effects. Venous malformations (VMs) are common congenital vascular malformations which are just characterized by the deficient quantity and abnormal function of vascular cells. However, the existence and role of VW-SCs in VMs is still unclear at present. In this study, the level and distribution of VW-SCs in 22 specimens of VMs were measured by immunochemistry, double-labeling immunofluorescence, and qPCR, followed by the Spearman rank correlation test. We found that both the protein and mRNA expression levels of CD34, vWF, VEGFR2, CD44, CD90, and CD105 were significantly downregulated in VMs compared with that in normal venules. VW-SCs were sporadically distributed or even absent within and outside the endothelium of VMs. The expression of the VW-SC-related markers was positively correlated with the density of both endothelial cells and perivascular cells. All those results and established evidence indicated that VW-SCs were more sporadically distributed with fewer amounts in VMs, which possibly contributing to the deficiency of vascular cells in VMs.

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Funding

This work was supported by the grants from the National Natural Science Foundation of China (81870783) to Prof. Yi-Fang Zhao, (81870361) to Prof. Gang Chen, and (82101036) to Dr. Hou-Fu Xia, and the Fundamental Research Funds for the Central Universities (2042021kf0186) to Dr. Hou-Fu Xia.

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Authors

Contributions

Hou-Fu Xia: conceptualization, data analysis, and manuscript preparation; Wen-Qiang Lai: immunohistochemistry, immunofluorescent staining, data analysis, and visualization; Gao-Hong Chen: collection and pretreatment of tissue specimens; Ye Li: immunohistochemistry, immunofluorescent staining, and data analysis; Qi-Hui Xie: RNA extraction and real-time qPCR; Yu-Lin Jia: collection of tissue specimens; Gang Chen and Yi-Fang Zhao: conceptualization and manuscript preparation.

Corresponding authors

Correspondence to Gang Chen or Yi-Fang Zhao.

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This study was approved by the review board of the ethics committee of the Hospital of Stomatology, Wuhan University (no. [2018]A22). The procedures were performed according to the National Institutes of Health guidelines regarding the use of human tissues.

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The authors declare no competing interests.

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Xia, HF., Lai, WQ., Chen, GH. et al. A histological study of vascular wall resident stem cells in venous malformations. Cell Tissue Res 390, 229–243 (2022). https://doi.org/10.1007/s00441-022-03672-3

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