A novel approach for studying mast cell–driven disorders: Mast cells derived from induced pluripotent stem cells - 03/03/22
, Frank Siebenhaar, MD a, e, ∗, Jörg Scheffel, PhD a, e, ⁎∗ 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.
Le texte complet de cet article est disponible en PDF.Key words : Mast cell, induced pluripotent stem cell, mast cell-driven disorder, disease-specific, patient-specific, urticaria, mastocytosis, allergy testing, drug screening
Abbreviations used : hiPSC, hiPSC-MC, HSC, hsMC, MC, MRGPRX2, PGD2, PSCMC
Plan
| This work was funded by GA2LEN (Global Allergy and Asthma European Network). |
|
| Data sharing statement: For original data, please contact yanyan.luo@charite.de as well as corresponding authors. |
|
| Disclosure of potential conflict of interest: M. Maurer is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Amgen, Aralez, ArgenX, AstraZeneca, Blueprint, Celldex, Centogene, CSL Behring, FAES, Genentech, GIInnovation, Innate Pharma, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Roche, Sanofi/Regeneron, Third HarmonicBio, UCB, and Uriach. F. Siebenhaar is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Blueprint, Celldex, Cogent Bio, Genentech, Glenmark, Moxie, Novartis, Pediapharm, Sanofi, and Uriach. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 3
P. 1060 - mars 2022 Retour au numéro
Article précédent
- TLR3-driven IFN-β antagonizes STAT5-activating cytokines and suppresses innate type 2 response in the lung
- Rinna Tei, Koji Iijima, Koji Matsumoto, Takao Kobayashi, Jyoti Lama, Elizabeth A. Jacobsen, Hirohito Kita
- Overactive WASp in X-linked neutropenia leads to aberrant B-cell division and accelerated plasma cell generation
- Minghui He, Mezida B. Saeed, Julien Record, Marton Keszei, Lia Gonçalves Pinho, Larissa Vasconcelos-Fontes, Roberta D’Aulerio, Rhaissa Vieira, Mariana M.S. Oliveira, Chiara Geyer, Lena Bohaumilitzky, Meike Thiemann, Ekaterina Deordieva, Lieselot Buedts, Joao Pedro Matias Lopes, Dmitry Pershin, Lennart Hammarström, Yu Xia, Xiaodong Zhao, Charlotte Cunningham-Rundles, Adrian J. Thrasher, Siobhan O. Burns, Vinicius Cotta-de-Almeida, Chaohong Liu, Anna Shcherbina, Peter Vandenberghe, Lisa S. Westerberg
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?