Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu-Hakola disease.

Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu-Hakola disease.
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DOI:
10.1038/srep04957
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发表时间:
2014-05-14
期刊:
影响因子:
4.6
通讯作者:
Kanba S
Kanba S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ohgidani M;Kato TA;Setoyama D;Sagata N;Hashimoto R;Shigenobu K;Yoshida T;Hayakawa K;Shimokawa N;Miura D;Utsumi H;Kanba S

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在啮齿动物和人类的死后研究中,小胶质细胞与各种神经和精神疾病有关。然而,由于缺乏对原位小胶质细胞的研究,小胶质细胞在活体人脑中的动态作用尚未明确。在此,我们提出了一种从人外周血细胞中培养诱导小胶质样细胞(iMG)的新技术。细胞因子、GM-CSF和IL-34的优化混合物在14天内将人单核细胞转化为iMG细胞。iMG细胞具有小胶质细胞特征;表达标记,形成分支形态,并与各种细胞因子释放吞噬活性。为了证实临床应用,我们从一名被认为是由小胶质细胞功能障碍直接引起的纳素-哈科拉病(NHD)患者身上提取了iMG细胞,并观察到与健康对照相比,NHD患者的这些细胞表达了延迟但更强的炎症反应。总之,img技术有望阐明人类小胶质细胞在各种脑部疾病中尚未解决的问题。
Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders.
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