诱导多能干细胞在疾病建模和药物发现中的应用。
Induced pluripotent stem cells in disease modelling and drug discovery.
机构信息
Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
出版信息
Nat Rev Genet. 2019 Jul;20(7):377-388. doi: 10.1038/s41576-019-0100-z.
Abstract
The derivation of induced pluripotent stem cells (iPSCs) over a decade ago sparked widespread enthusiasm for the development of new models of human disease, enhanced platforms for drug discovery and more widespread use of autologous cell-based therapy. Early studies using directed differentiation of iPSCs frequently uncovered cell-level phenotypes in monogenic diseases, but translation to tissue-level and organ-level diseases has required development of more complex, 3D, multicellular systems. Organoids and human-rodent chimaeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer.
摘要
十多年前，诱导多能干细胞（iPSC）的出现引发了人们广泛的热情，希望开发人类疾病的新模型、改进药物发现平台，并更广泛地应用自体细胞疗法。早期使用 iPSC 的定向分化研究经常在单基因疾病中发现细胞水平的表型，但要将其转化为组织和器官水平的疾病，就需要开发更复杂的、三维的、多细胞系统。类器官和人-鼠嵌合体更准确地模拟了复杂组织的多样化细胞生态系统，正被应用于 iPSC 疾病模型，以重现广泛的人类疾病的病理生物学，包括传染病、遗传疾病和癌症。
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