Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
Estimating the concentration of therapeutic range using disease-specific iPS cells: Low-dose rapamycin therapy for Pendred syndrome
复制标题
使用疾病特异性 iPS 细胞估计治疗范围的浓度：低剂量雷帕霉素治疗 Pendred 综合征
DOI：
10.1016/j.reth.2018.11.001
复制
发表时间：
2018
期刊：
影响因子：
4.3
通讯作者：
Ogawa K.
中科院分区：
文献类型：
--
作者：
Hosoya M;Saeki T;Saegusa C;Matsunaga T;Okano H;Fujioka M;Ogawa K.
Pendred综合征是一种常染色体隐性遗传疾病，以先天性听力损失和甲状腺肿大为特征。以前，细胞应激敏感性被证明增加患者来源的细胞与细胞内聚集使用体外急性耳蜗细胞模型来自患者特异性多能干细胞（iPS）。此外，我们发现雷帕霉素可以减轻细胞死亡。然而，关于长期的细胞生存没有细胞应激源，模仿自然病程的疾病或合理的最低浓度的雷帕霉素，防止细胞deathsmissing.MethodsIn这份报告中，我们首先调查了合理的最低浓度的雷帕霉素使用患者特异性的iPS细胞衍生的耳蜗细胞与三种不同条件的急性应激。接下来，我们证实了雷帕霉素的影响，在长期的细胞存活和表型，通过使用耳蜗细胞来自三个不同的患者来源的iPS cells.ResultsWe发现，内耳细胞来自Pendred综合征患者是更脆弱的比那些从健康的人在长期培养，然而，这种易感性通过治疗与低剂量雷帕霉素缓解。患者听力损失进展缓慢，部分原因可能是在长期培养过程中观察到患者细胞的脆弱性。我们成功地评估了合理的最低浓度的雷帕霉素治疗Pendred syndrome.ConclusionOur结果表明，低剂量的雷帕霉素不仅可以减少急性症状，但可能会阻止听力损失的进展Pendred综合征患者。
IntroductionPendred syndrome is an autosomal-recessive disease characterized by congenital hearing loss and thyroid goiter. Previously, cell stress susceptibilities were shown to increase in patient-derived cells with intracellular aggregation using anin vitroacute cochlear cell model derived from patient-specific pluripotent stem (iPS) cells. Moreover, we showed that rapamycin can relieve cell death. However, studies regarding long-term cell survival without cell stressors that mimic the natural course of disease or the rational minimum concentration of rapamycin that prevents cell death are missing.MethodsIn this report, we first investigated the rational minimum concentration of rapamycin using patient-specific iPS cells derived-cochlear cells with three different conditions of acute stress. We next confirmed the effects of rapamycin in long-term cell survival and phenotypes by using cochlear cells derived from three different patient-derived iPS cells.ResultsWe found that inner ear cells derived from Pendred syndrome patients are more vulnerable than those from healthy individuals during long-term culturing; however, this susceptibility was relieved via treatment with low-dose rapamycin. The slow progression of hearing loss in patients may be explained, in part, by the vulnerability observed in patient cells during long-term culturing. We successfully evaluated the rational minimum concentration of rapamycin for treatment of Pendred syndrome.ConclusionOur results suggest that low-dose rapamycin not only decreases acute symptoms but may prevent progression of hearing loss in Pendred syndrome patients.
登录
查看更多内容
影响因子：
23.9
作者：
通讯作者：
--
使用疾病特异性 iPSC 进行耳蜗细胞建模揭示了退行性表型和先天性进行性听力损失的治疗方法
DOI：
--
发表时间：
2017
期刊：
影响因子：
--
作者：
Makoto Hosoya、Masato Fujioka ;Tatsuo Matsunaga ;Kaoru Ogawa ,
通讯作者：
Kaoru Ogawa ,
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT
DOI：
10.1056/nejmoa1100391
发表时间：
2011-04-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
McCormack FX;Inoue Y;Moss J;Singer LG;Strange C;Nakata K;Barker AF;Chapman JT;Brantly ML;Stocks JM;Brown KK;Lynch JP 3rd;Goldberg HJ;Young LR;Kinder BW;Downey GP;Sullivan EJ;Colby TV;McKay RT;Cohen MM;Korbee L;Taveira-DaSilva AM;Lee HS;Krischer JP;Trapnell BC;National Institutes of Health Rare Lung Diseases Consortium;MILES Trial Group
通讯作者：
MILES Trial Group
先天性耳聋与甲状腺肿（潘德雷德氏综合症）的关联：一项针对 207 个家庭的研究
影响因子：
1.9
作者：
B. G. R. Fraser
通讯作者：
B. G. R. Fraser