Differentiation and Functional Comparison of Monocytes and Macrophages from hiPSCs with Peripheral Blood Derivatives
Differentiation and Functional Comparison of Monocytes and Macrophages from hiPSCs with Peripheral Blood Derivatives
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DOI：
10.1016/j.stemcr.2019.05.003
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发表时间：
2019-06-11
影响因子：
5.9
通讯作者：
Orlova, Valeria V.
中科院分区：
文献类型：
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作者：
Cao, Xu;Yakala, Gopala K.;Orlova, Valeria V.
人类单核细胞和巨噬细胞的再生来源将是生物医学研究中有价值的替代外周血原代细胞的来源。我们开发了一种从人诱导多能干细胞（hiPSCs）中提取单核细胞和巨噬细胞的有效方案，并与pb来源的细胞进行了功能比较。hipsc衍生的单核细胞在冷冻保存后具有功能，其基因表达谱与pb衍生的单核细胞相当。值得注意的是，在生理流动下，hipsc衍生的单核细胞更活跃，与内皮细胞的粘附更强。hipsc来源的单核细胞成功极化为M1和M2型巨噬细胞，其泛型和亚型特异性基因和表面蛋白的表达以及细胞因子的分泌与pb来源的巨噬细胞相似。hipsc衍生的巨噬细胞表现出更高的内吞和efferocysis功能，并且与pb衍生的巨噬细胞具有相似的细菌和肿瘤细胞吞噬功能。总之，我们开发了一种强大的方案，从独立的hiPSC系中产生hiPSC单核细胞和巨噬细胞，这些细胞显示出与PB相当的功能成熟度。
A renewable source of human monocytes and macrophages would be a valuable alternative to primary cells from peripheral blood (PB) in biomedical research. We developed an efficient protocol to derive monocytes and macrophages from human induced pluripotent stem cells (hiPSCs) and performed a functional comparison with PB-derived cells. hiPSC-derived monocytes were functional after cryopreservation and exhibited gene expression profiles comparable with PB-derived monocytes. Notably, hiPSC-derived monocytes were more activated with greater adhesion to endothelial cells under physiological flow. hiPSC-derived monocytes were successfully polarized to M1 and M2 macrophage subtypes, which showed similar pan- and subtype-specific gene and surface protein expression and cytokine secretion to PB-derived macrophages. hiPSC-derived macrophages exhibited higher endocytosis and efferocytosis and similar bacterial and tumor cell phagocytosis to PB-derived macrophages. In summary, we developed a robust protocol to generate hiPSC monocytes and macrophages from independent hiPSC lines that showed aspects of functional maturity comparable with those from PB.