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Luo Y, Fernandez Vallone V, He J, et al. A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells. J Allergy Clin Immunol. 2021;doi: 10.1016/j.jaci.2021.07.027.
Luo, Y., Fernandez Vallone, V., He, J., Frischbutter, S., Kolkhir, P., Moñino-Romero, S., Stachelscheid, H., Streu-Haddad, V., Maurer, M., Siebenhaar, F., & Scheffel, J. (2021). A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells. The Journal of allergy and clinical immunology, . https://doi.org/10.1016/j.jaci.2021.07.027
Luo, Yanyan, et al. "A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells." The Journal of allergy and clinical immunology vol. (2021). doi: https://doi.org/10.1016/j.jaci.2021.07.027
Luo Y, Fernandez Vallone V, He J, Frischbutter S, Kolkhir P, Moñino-Romero S, Stachelscheid H, Streu-Haddad V, Maurer M, Siebenhaar F, Scheffel J. A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells. J Allergy Clin Immunol. 2021 Aug 08; doi: 10.1016/j.jaci.2021.07.027. Epub 2021 Aug 08. PMID: 34371081.
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J Allergy Clin Immunol. 2021 Aug 08; doi: 10.1016/j.jaci.2021.07.027. Epub 2021 Aug 08.

A novel approach for studying mast cell-driven disorders: Mast cells derived from induced pluripotent stem cells.

The Journal of allergy and clinical immunology

Yanyan Luo, Valeria Fernandez Vallone, Jiajun He, Stefan Frischbutter, Pavel Kolkhir, Sherezade Moñino-Romero, Harald Stachelscheid, Viktoria Streu-Haddad, Marcus Maurer, Frank Siebenhaar, Jörg Scheffel

Affiliations

  1. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
  2. Charité-BIH Centrum Therapy and Research, BIH Stem Cell Core Facility, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  3. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, China; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
  4. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; I.M. Sechenov First Moscow State Medical University (Sechenov University), Division of Immune-mediated Skin Diseases, Moscow, Russia; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
  5. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany. Electronic address: [email protected].
  6. Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany. Electronic address: [email protected].

PMID: 34371081 DOI: 10.1016/j.jaci.2021.07.027

Abstract

BACKGROUND: Mast cells (MCs) are considered the main effectors in allergic reactions and well known for their contribution to the pathogenesis of various inflammatory diseases, urticaria, and mastocytosis. To study their functions in vitro, human primary MCs are isolated directly from several tissues or differentiated from hematopoietic progenitors. However, these techniques bear several disadvantages and challenges including low proliferation capacity, donor-dependent heterogeneity, and the lack of a continuous cell source.

OBJECTIVE: To address this, we developed a novel strategy for the rapid and efficient differentiation of MCs from human-induced pluripotent stem cells (hiPSCs).

METHODS: A 4-step protocol for the generation of hiPSC-derived MCs, based on the use of 3 hiPSC lines, was established and validated by comparison with human skin MCs and peripheral hematopoietic stem cell-derived MCs.

RESULTS: hiPSC-MCs share phenotypic and functional characteristics of human skin MCs and peripheral hematopoietic stem cell-derived MCs. They display stable expression of the MC-associated receptors CD117, FcεRIα, and Mas-related G protein-coupled receptor X2 and degranulate in response to IgE/anti-IgE and substance P.

CONCLUSIONS: This novel hiPSC-based approach provides a sustainable and homogeneous source for a rapid and highly productive generation of phenotypically mature, functional MCs, and its principle allows for the investigation of disease- and patient-specific MC populations.

Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Keywords: Mast cell; allergy testing; disease-specific; drug screening; induced pluripotent stem cell; mast cell-driven disorder; mastocytosis; patient-specific; urticaria

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