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Biomaterials. 2018 Mar;158:34-43. doi: 10.1016/j.biomaterials.2017.12.014. Epub 2017 Dec 16.

VE-Cadherin regulates the self-renewal of mouse embryonic stem cells via LIF/Stat3 signaling pathway.

Author information

1
Nankai University School of Medicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Science, Tianjin, China; Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, China.
2
State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China; Department of Ophthalmology, Ophthalmology and Visual Science Key Lab of PLA, Chinese PLA General Hospital, Beijing, China.
3
Nankai University School of Medicine, Tianjin, China.
4
State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Science, Tianjin, China.
5
State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China.
6
Department of Hepato-Gastroenterology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China.
7
Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing, China.
8
Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China.
9
State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Science, Tianjin, China. Electronic address: yangjun106@nankai.edu.cn.
10
Nankai University School of Medicine, Tianjin, China; State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Science, Tianjin, China; State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China. Electronic address: zongjinli@nankai.edu.cn.

Abstract

With the abilities of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for stem cell-based therapeutics. However, the maintenance of ES cells with mouse embryonic fibroblasts (MEFs) can limit the clinical translation of ES cells. In the present study, we synthesized a fusion protein of the immunoglobulin G (IgG) fragment crystallizable region and vascular endothelial cadherin (VE-cadherin) extracellular domain (VE-cad-Fc) as a substrate for mouse ES cell culture, and we hypothesized that VE-cadherin could enhance the pluripotency and self-renewal of ES cells. Furthermore, we introduced a Stat3 reporter imaging system into ES cells and investigated the mechanism of the pluripotency enhancement mediated by VE-cadherin through cultured ES cells on VE-cad-Fc-coated plates using molecular imaging techniques. The resulting data revealed that VE-cad-Fc could activate the Stat3 signaling pathway, leading to the upregulation of stemness-related markers SSEA-1 and alkaline phosphatase (ALP). Moreover, VE-cad-Fc recovered the expression of Oct4, c-Myc, Nanog, Sox2, Tbx3 and Klf4 in differentiated ES cells, as well as enhanced the pluripotency of ES cells. In conclusion, VE-cadherin fusion protein coating methods provide an alternative towards feeder free culture of ES cells, and the strategy developed in the present study may benefit the clinical translation of ES cell-based therapeutics.

KEYWORDS:

Differentiation; Embryonic stem cell; Pluripotency; Self-renewal; Stat3; VE-cadherin

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