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高产量的人诱导多能干细胞来源的单核细胞和巨噬细胞在功能上与原代细胞相当。

High-Yield Human Induced Pluripotent Stem Cell-Derived Monocytes and Macrophages Are Functionally Comparable With Primary Cells.

作者信息

Cui Di, Franz Alexandra, Fillon Sophie A, Jannetti Linda, Isambert Timo, Fundel-Clemens Katrin, Huber Heinrich J, Viollet Coralie, Ghanem Alexander, Niwa Akira, Weigle Bernd, Pflanz Stefan

机构信息

Boehringer Ingelheim Pharma GmbH & Co. KG, Cancer Immunology and Immune Modulation, Biberach an der Riss, Germany.

Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, Biberach an der Riss, Germany.

出版信息

Front Cell Dev Biol. 2021 Apr 13;9:656867. doi: 10.3389/fcell.2021.656867. eCollection 2021.

DOI:10.3389/fcell.2021.656867
PMID:33937256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8080307/
Abstract

Macrophages are pivotal effectors of host immunity and regulators of tissue homeostasis. Understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (hiPSC)-derived monocytes and macrophages, as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of macrophage biology and implication in human diseases. In this study, we present a fully optimized differentiation protocol of hiPSC-derived monocytes and granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF). We present characterization of iPSC-derived myeloid lineage cells at phenotypic, functional, and transcriptomic levels, in comparison with corresponding subsets of peripheral blood-derived cells. We also highlight the application of hiPSC-derived monocytes and macrophages as a gene-editing platform for functional validation in research and drug screening, and the study also provides a reference for cell therapies.

摘要

巨噬细胞是宿主免疫的关键效应细胞和组织稳态的调节因子。由于缺乏用于细胞和基因研究的可靠且可扩展的模型，对人类巨噬细胞生物学的理解受到了阻碍。人类诱导多能干细胞（hiPSC）衍生的单核细胞和巨噬细胞，作为特定个体基因型细胞的无限来源，无疑将在推进我们对巨噬细胞生物学的理解以及其在人类疾病中的意义方面发挥重要作用。在本研究中，我们展示了一种针对hiPSC衍生的单核细胞以及粒细胞-巨噬细胞集落刺激因子（GM-CSF）或巨噬细胞集落刺激因子（M-CSF）的完全优化的分化方案。我们展示了与外周血来源细胞的相应亚群相比，iPSC衍生的髓系谱系细胞在表型、功能和转录组水平上的特征。我们还强调了hiPSC衍生的单核细胞和巨噬细胞作为用于研究和药物筛选中功能验证的基因编辑平台的应用，并且该研究也为细胞治疗提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beec/8080307/d47e3481cbbe/fcell-09-656867-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beec/8080307/0d4a63913c5b/fcell-09-656867-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beec/8080307/d47e3481cbbe/fcell-09-656867-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beec/8080307/0d4a63913c5b/fcell-09-656867-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beec/8080307/ceb03143fda8/fcell-09-656867-g002.jpg
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