Mesenchymal stem cells promote lymphangiogenic properties of lymphatic endothelial cells

Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not bee...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2018-08, Vol.22 (8), p.3740-3750
Main Authors: Robering, Jan W., Weigand, Annika, Pfuhlmann, Romy, Horch, Raymund E., Beier, Justus P., Boos, Anja M.
Format: Article
Language:English
Subjects:
Angiogenesis
Assaying
Cancer
Capillary tubes
Cell culture
Cell migration
Cell proliferation
Collagen
Conditioning
Endothelial cells
Fibrin
Fibroblast growth factor 2
Gels
Growth factors
lymphangiogenesis
lymphatic endothelial cells
Medical prognosis
Mesenchymal stem cells
Mesenchyme
Metastases
Molecular chains
Molecular modelling
Original
Secretome
Spheroids
Stem cells
Stimulation
Vascular endothelial growth factor
Wound healing
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Summary:Lymphatic metastasis is one of the main prognostic factors concerning long‐term survival of cancer patients. In this regard, the molecular mechanisms of lymphangiogenesis are still rarely explored. Also, the interactions between stem cells and lymphatic endothelial cells (LEC) in humans have not been well examined. Therefore, the main objective of this study was to assess the interactions between mesenchymal stem cells (MSC) and LEC using in vitro angiogenesis assays. Juvenile LEC were stimulated with VEGF‐C, bFGF, MSC‐conditioned medium (MSC‐CM) or by co‐culture with MSC. LEC proliferation was assessed using a MTT assay. Migration of the cells was determined with a wound healing assay and a transmigration assay. To measure the formation of lymphatic sprouts, LEC spheroids were embedded in collagen or fibrin gels. The LEC's capacity to form capillary‐like structures was assessed by a tube formation assay on Matrigel®. The proliferation, migration and tube formation of LEC could be significantly enhanced by MSC‐CM and by co‐culture with MSC. The effect of stimulation with MSC‐CM was stronger compared to stimulation with the growth factors VEGF‐C and bFGF in proliferation and transmigration assays. Sprouting was stimulated by VEGF‐C, bFGF and by MSC‐CM. With this study, we demonstrate the potent stimulating effect of the MSC secretome on proliferation, migration and tube formation of LEC. This indicates an important role of MSC in lymphangiogenesis in pathological as well as physiological processes.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.13590