Involvement of Macrophages in the Pathogenesis of Familial Amyloid Polyneuropathy and Efficacy of Human iPS Cell-Derived Macrophages in Its Treatment.
Involvement of Macrophages in the Pathogenesis of Familial Amyloid Polyneuropathy and Efficacy of Human iPS Cell-Derived Macrophages in Its Treatment.
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DOI：
10.1371/journal.pone.0163944
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ando Y
中科院分区：
文献类型：
--
作者：
Suenaga G;Ikeda T;Komohara Y;Takamatsu K;Kakuma T;Tasaki M;Misumi Y;Ueda M;Ito T;Senju S;Ando Y
我们假设家族性淀粉样蛋白多发性神经病变（FAP）患者的组织内巨噬细胞将表现出定性或定量异常，这可能加速甲状腺素（TTR）衍生的淀粉样蛋白沉积。为了评估这一点，我们检查了淀粉样蛋白沉积FAP患者和对照患者心脏组织中组织常驻巨噬细胞的数量和亚群。在FAP和对照组患者中，心脏组织中的组织常驻巨噬细胞均为Iba+/CD163+/CD206+巨噬细胞。然而，与对照组相比，FAP患者的巨噬细胞数量明显减少。此外，与健康供者相比，外周血中CD14+单核细胞细胞内TTR的比例降低。基于这些结果，我们接下来研究了TTR在人类诱导多能干细胞衍生的髓系细胞（MLs）中的降解和内吞作用，其功能类似巨噬细胞。iPS-MLs表达CD163和CD206，属于抑制性巨噬细胞类别。此外，iPS-MLs在体外以细胞依赖的方式降解天然和聚集的TTR。此外，ips - ml内吞糖聚集，特别是聚合，TTR。这些结果表明，组织定位的巨噬细胞减少破坏了ttr来源的淀粉样蛋白沉积的清除，导致FAP患者病理状况的进展。为了改善这种情况，临床应用多能干细胞来源的MLs可能是一种有用的FAP治疗方法。
We hypothesized that tissue-resident macrophages in familial amyloid polyneuropathy (FAP) patients will exhibit qualitative or quantitative abnormalities, that may accelerate transthyretin (TTR)-derived amyloid deposition. To evaluate this, we examined the number and subset of tissue-resident macrophages in heart tissue from amyloid-deposited FAP and control patients. In both FAP and control patients, tissue-resident macrophages in heart tissue were all Iba+/CD163+/CD206+ macrophages. However, the number of macrophages was significantly decreased in FAP patients compared with control patients. Furthermore, the proportion of intracellular TTR in CD14+ monocytes was reduced in peripheral blood compared with healthy donors. Based on these results, we next examined degradation and endocytosis of TTR in human induced pluripotent stem (iPS) cell-derived myeloid lineage cells (MLs), which function like macrophages. iPS-MLs express CD163 and CD206, and belong to the inhibitory macrophage category. In addition, iPS-MLs degrade both native and aggregated TTR in a cell-dependent manner in vitro. Further, iPS-MLs endocytose aggregated, and especially polymerized, TTR. These results suggest that decreased tissue-localized macrophages disrupt clearance of TTR-derived amyloid deposits, leading to progression of a pathological condition in FAP patients. To improve this situation, clinical application of pluripotent stem cell-derived MLs may be useful as an approach for FAP therapy.
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影响因子：
5.3
作者：
Gray EE;Cyster JG
通讯作者：
Cyster JG
影响因子：
4.4
作者：
Hawkins PN;Ando Y;Dispenzeri A;Gonzalez-Duarte A;Adams D;Suhr OB
通讯作者：
Suhr OB
DOI：
10.1006/bbrc.1996.1112
发表时间：
1996-07-25
影响因子：
3.1
作者：
Imai, Y;Ibata, I;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
20.3
作者：
Buehler, Paul W.;Abraham, Bindu;Schaer, Dominik J.
通讯作者：
Schaer, Dominik J.
影响因子：
15.9
作者：
KANAI, M;RAZ, A;GOODMAN, DS
通讯作者：
GOODMAN, DS