ArticlePloS one2015
Aberrant lymphatic endothelial progenitors in lymphatic malformation development.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Identification of pathological CD133+ endothelial cells in venous malformations.Frontiers in cardiovascular medicine · 2026Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- Upregulated MicroRNA-21 Drives the Proliferation of Lymphatic Malformation Endothelial Cells by Inhibiting PDCD4.The Journal of investigative dermatology · 2023Article
- Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.Journal of vascular anomalies · 2023Review
- Cervical lymphangioma in adults: A report of seven cases and review of the literature.Laryngoscope investigative otolaryngology · 2022Article
- Vanishing Lymphocytes in a Case of Vanishing Bone Disease.Journal of clinical immunology · 2022Article
- Article
- Lymphatic Endothelial Cell Defects in Congenital Cardiac Patients With Postoperative Chylothorax.Journal of vascular anomalies · 2021Article
- Clinical Assessment and Lesion-Specific Management of Orbital Vascular Malformations.Journal of neurological surgery. Part B, Skull base · 2021Article
- Recent Progress in Lymphangioma.Frontiers in pediatrics · 2021Review
- Stemness-Associated Markers Are Expressed in Extracranial Arteriovenous Malformation.Frontiers in surgery · 2021Article
- Cell Populations Expressing Stemness-Associated Markers in Vascular Anomalies.Frontiers in surgery · 2020Review
- Myeloid-Derived Lymphatic Endothelial Cell Progenitors Significantly Contribute to Lymphatic Metastasis in Clinical Breast Cancer.The American journal of pathology · 2019Article
- Cellular and molecular mechanisms of PIK3CA-related vascular anomalies.Vascular biology (Bristol, England) · 2019Review
- New Approach to Rare Pediatric Multicystic Mesenteric Lymphangioma; Would It Guide the Development of Targeted Therapy?Frontiers in pediatrics · 2018Article
- Article
- Article
- Basic fibroblast growth factor promotes VEGF-C-dependent lymphangiogenesis via inhibition of miR-381 in human chondrosarcoma cells.Oncotarget · 2016Article
- Pediatric lymphatic malformations: evolving understanding and therapeutic options.Pediatric surgery international · 2016Review
- WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.
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Registered trials
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