Application of iPSC to Modelling of Respiratory Diseases.

Application of iPSC to Modelling of Respiratory Diseases.
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DOI:
10.1007/5584_2019_430
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发表时间:
2020
影响因子:
--
通讯作者:
Ryan Firth AL
Ryan Firth AL
中科院分区:
医学4区
文献类型:
--
作者:
Calvert BA;Ryan Firth AL

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呼吸系统疾病是世界范围内发病率和死亡率的主要原因之一,随着老年人口的普遍存在,发病率不断增加。许多肺部疾病的治疗是为了缓解症状,没有治愈方法,这表明迫切需要新的治疗策略。这些进展受到缺乏对人类肺部病理学如何启动和进展的理解的阻碍。对人类肺部疾病的研究依赖于从受损的肺中分离原代细胞或使用永生化细胞,这两种方法在代表人群中基因组和表型变异性的能力方面都是有限的。在一个我们正在向精准医学发展的时代,使用患者特异性诱导多能细胞(iPSC)来生成模型,其中足够的原代细胞和组织稀缺,增加了我们理解人类肺部病理生理学的能力。iPSC向肺的定向分化提出了在产生iPSC衍生的肺上皮细胞中要克服的最初挑战。从那时起,在定义用于指定和分离特定肺谱系的方案方面取得了重大进展,现在可以生成气道球状体和多细胞类器官。这一技术进步为人类肺部研究和自体细胞治疗开辟了前景。本章将重点介绍iPSC在研究人类肺部疾病中的应用。
Respiratory disease is one of the leading causes of morbidity and mortality world-wide with an increasing incidence as the aged population prevails. Many lung diseases are treated for symptomatic relief, with no cure available, indicating a critical need for novel therapeutic strategies. Such advances are hampered by a lack of understanding of how human lung pathologies initiate and progress. Research on human lung disease relies on the isolation of primary cells from explanted lungs or the use of immortalized cells, both are limited in their capacity to represent the genomic and phenotypic variability among the population. In an era where we are progressing toward precision medicine the use of patient specific induced pluripotent cells (iPSC) to generate models, where sufficient primary cells and tissues are scarce, has increased our capacity to understand human lung pathophysiology. Directed differentiation of iPSC toward lung presented the initial challenge to overcome in generating iPSC-derived lung epithelial cells. Since then major advances have been made in defining protocols to specify and isolate specific lung lineages, with the generation of airway spheroids and multi cellular organoids now possible. This technological advance has opened up our capacity for human lung research and prospects for autologous cell therapy. This chapter will focus on the application of iPSC to studying human lung disease.
人类肺发育和疾病的三维模型来自多能干细胞。
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