BMP-4 and VEGF promote development of hematopoietic stem cells during the embryoid body formation from embryonic stem cells.
- Author:
Hui-Qin CHEN
1
;
Xu-Chao ZHANG
;
Shao-Liang HUANG
;
Yun CAI
;
Bei-Yan WU
;
Dun-Hua ZHOU
;
Ke HUANG
Author Information
1. Department of Pediatrics, The Third Hospital, SUN Yat-sen University, Guangzhou 510630, Guangdong Province, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Morphogenetic Protein 4;
pharmacology;
Cell Differentiation;
drug effects;
Cells, Cultured;
Embryonic Stem Cells;
cytology;
drug effects;
Hematopoietic Stem Cells;
cytology;
Mice;
Vascular Endothelial Growth Factors;
pharmacology
- From:
Journal of Experimental Hematology
2008;16(4):855-858
- CountryChina
- Language:Chinese
-
Abstract:
The objective of this study was to explore the effects of BMP-4 and VEGF on the development of primary hematopoietic stem cells during the differentiation of embryonic stem cells (ESCs) into embryoid body (EB). Murine E14 ESCs were seeded into semisolid methylcellulose-based medium for EB formation. According to added or not cytokines, experiments were divided into: (1) group of spontaneous differentiation without cytokine as control; (2) group of BMP-4 in different concentrations (0, 5, 15, 25 and 50 ng/ml); (3) group of BMP-4 combined with VEGF; (4) group of VEGF alone. EBs were collected on days 3, 6, 9, 12, 15, and the proportion of Flk-1(+) cells were assayed by flow cytometry. The results showed that in the different BMP-4 concentration groups, the proportions of Flk-1(+) cells were significantly different, and it reached the peak values in 25 ng/ml BMP-4 group as 6.51 +/- 1.02% at day 3 and 7.70 +/- 1.12% at day 6 respectively, which were statistically higher than those in control group without-BMP-4 and in 5 ng/ml BMP-4 group (p < 0.05). When BMP-4 was used in combination with VEGF, Flk-1(+) cells went to peak proportion value at day 9 as 27.53 +/- 8.14%, which was statistically higher than that in spontaneous differentiation group as 8.77 +/- 2.35% (p < 0.05) and VEGF treatment group as 11.21 +/- 2.23% (p < 0.05). It is concluded that BMP-4 in combination with VEGF can promote Flk-1(+) cells genesis during EB formation in vitro, which provides experimental evidence for researches on directed differentiation of ESCs into hematopoietic stem cells simulating the microenvironment in vivo.