Direct development of functionally mature tryptase/chymase double-positive connective tissue-type mast cells from primate embryonic stem cells

作者：Ma Feng; Kambe Naotomo; Wang Dan; Shinoda Gen; Fujino Hisanori; Umeda Katsutsugu; Fujisawa Akihiro; Ma Lina; Suemori Hirofumi; Nakatsuji Norio; Miyachi Yoshiki; Torii Ryuzo; Tsuji Kohichiro; Heike Toshio; Nakahataa Tatsutoshi^*

来源：Stem Cells, 2008, 26(3): 706-714.

DOI：10.1634/stemcells.2007-0348

• embryonic stem cells
• mast cells
• primate
• development
• chymase
• tryptase

Conditions that influence the selective development or recruitment of connective tissue-type and mucosal-type mast cells (MCs) are not well understood. Here, we report that cynomolgus monkey embryonic stem (ES) cells cocultured with the murine aorta-gonad-mesonephros-derived stromal cell line AGM-S1 differentiated into cobblestone (CS)-like cells by day 10-15. When replated onto fresh AGM-S1 with the addition of stem cell factor, interleukin-6, and Flt3 ligand, these CS-like cells displayed robust growth and generated almost 100% tryptase/chymase double-positive MCs within 3 weeks. At all time points, the percentage of tryptase-positive cells did not exceed that of chymase-positive cells. These ES-derived MCs were CD45+/Kit+/CD31+/CD203c+/HLA-DR- and coexpressed a high-affinity IgE receptor on their surface, which was upregulated after IgE exposure. Electron microscopy showed that they contained many electron dense granules. Moreover, ES-derived MCs responded to stimulation by via IgE and substance P by releasing histamine. These results indicate that ES-derived MCs have the phenotype of functionally mature connective tissue-type MCs. The rapid maturation of ES-derived MCs suggests a unique embryonic pathway in primates for early development of connective tissue-type MCs, which may be independent from the developmental pathway of mucosal-type MCs.

• 出版日期2008
• 单位河北医科大学