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.

中文翻译：

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一种研究肥大细胞驱动疾病的新方法：源自诱导多能干细胞的肥大细胞

背景

肥大细胞 (MCs) 被认为是过敏反应的主要效应物，并因其对各种炎症性疾病、荨麻疹和肥大细胞增多症的发病机制的贡献而广为人知。为了在体外研究它们的功能，人类原发性 MC 直接从几种组织中分离出来或从造血祖细胞中分化出来。然而，这些技术存在一些缺点和挑战，包括低增殖能力、依赖供体的异质性以及缺乏连续的细胞来源。

客观的

为了解决这个问题，我们开发了一种新的策略，用于快速有效地将 MCs 从人类诱导的多能干细胞 (hiPSCs) 中分化出来。

方法

通过与人类皮肤 MCs 和外周造血干细胞衍生的 MCs 进行比较，建立并验证了基于使用 3 个 hiPSC 系的 hiPSC 衍生 MCs 生成的 4 步方案。

结果

hiPSC-MCs 具有人类皮肤 MCs 和外周造血干细胞衍生 MCs 的表型和功能特征。它们表现出 MC 相关受体 CD117、FcεRIα 和 Mas 相关 G 蛋白偶联受体 X2 的稳定表达，并响应 IgE/抗 IgE 和 P 物质而脱粒。

结论

这种基于 hiPSC 的新型方法为快速、高效地生成表型成熟的功能性 MCs 提供了可持续和同质的来源，其原理允许研究疾病和患者特异性 MC 群体。