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EMBRYONIC STEM CELLS

Direct Development of Functionally Mature Tryptase/Chymase Double-Positive Connective Tissue-Type Mast Cells from Primate Embryonic Stem Cells

Departments of ^aPediatrics and
^cDermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan;
^bDivision of Cellular Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
^dResearch Center for Regenerative Medicine, Kyoto University, Kyoto, Japan;
^eResearch Center for Animal Life Science, Shiga University of Medical Science, Ohtsu, Japan;
^fDepartment of Dermatology, Chiba University Graduate School of Medicine, Chiba, Japan

Key Words. Embryonic stem cells • Mast cells • Primate • Development • Chymase • Tryptase

Correspondence: Tatsutoshi Nakahata, M.D., Ph.D., Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Telephone: 81-75-751-3290; Fax: 81-75-752-2361; e-mail: tnakaha{at}kuhp.kyoto-u.ac.jp

Received May 8, 2007; accepted for publication October 25, 2007.
First published online in STEM CELLS EXPRESS   November 8, 2007.



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.

Disclosure of potential conflicts of interest is found at the end of this article.

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				F. Ma, Y. Ebihara, K. Umeda, H. Sakai, S. Hanada, H. Zhang, Y. Zaike, E. Tsuchida, T. Nakahata, H. Nakauchi, et al. Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis PNAS, September 2, 2008; 105(35): 13087 - 13092. [Abstract] [Full Text] [PDF]