CD 34 + VEGFR ‐3 + progenitor cells have a potential to differentiate towards lymphatic endothelial cells

• Published in: Journal of cellular and molecular medicine Vol. 18; no. 3; pp. 422 - 433
• Main Authors: Tan, Yu‐zhen, Wang, Hai‐jie, Zhang, Mei‐hua, Quan, Zhe, Li, Ting, He, Qi‐zhi
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Inc 01.03.2014
• Subjects: Antigens; Bone marrow; CD34 antigen; CD44 antigen; Cell differentiation; Cell proliferation; Collagen; Colonies; Cord blood; Endothelial cells; Extracellular matrix; Fluorescence; Gene expression; Growth factors; Hyaluronic acid; Lasers; Leukocytes (mononuclear); Lymphatic system; Metastasis; Nucleotidase; Phenotypes; Progenitor cells; Signal transduction; siRNA; Stem cells; Transplantation; Umbilical cord; Vascular endothelial growth factor; Vascular endothelial growth factor receptors; Vascularization; United States > US
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.12233

Abstract Endothelial progenitor cells ( EPC s) play an important role in postnatal neovascularization. However, it is poorly understood whether EPC s contribute to lymphangiogenesis. Here, we assessed differentiation of a novel population of EPC s towards lymphatic endothelial cells and their lymphatic formation. CD 34 + VEGFR ‐3 + EPC s were isolated from mononuclear cells of human cord blood by fluorescence‐activated cell sorting. These cells expressed CD 133 and displayed the phenotype of the endothelial cells. Cell colonies appeared at 7–10 days after incubation. The cells of the colonies grew rapidly and could be repeatedly subcultured. After induction with VEGF ‐C for 2 weeks, CD 34 + VEGFR ‐3 + EPC s could differentiate into lymphatic endothelial cells expressing specific markers 5′‐nucleotidase, LYVE ‐1 and Prox‐1. The cells also expressed hyaluronan receptor CD 44. The differentiated cells had properties of proliferation, migration and formation of lymphatic capillary‐like structures in three‐dimensional collagen gel and Matrigel. VEGF ‐C enhanced VEGFR ‐3 m RNA expression. After interfering with VEGFR ‐3 si RNA , the effects of VEGF ‐C were diminished. These results demonstrate that there is a population of CD 34 + VEGFR ‐3 + EPC s with lymphatic potential in human cord blood. VEGF ‐C/ VEGFR ‐3 signalling pathway mediates differentiation of CD 34 + VEGFR ‐3 + EPC s towards lymphatic endothelial cells and lymphangiogenesis. Cord blood‐derived CD 34 + VEGFR ‐3 + EPC s may be a reliable source in transplantation therapy for lymphatic regenerative diseases.