Department of Pediatrics - Division of Neonatal-Perinatal Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Departments of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Pediatr Res. 2018 Oct;84(4):499-508. doi: 10.1038/s41390-018-0064-2. Epub 2018 May 30.
The study of disease pathophysiology has long relied on model systems, including animal models and cultured cells. In 2006, Shinya Yamanaka achieved a breakthrough by reprogramming somatic cells into induced pluripotent stem cells (iPSCs). This revolutionary discovery provided new opportunities for disease modeling and therapeutic intervention. With established protocols, investigators can generate iPSC lines from patient blood, urine, and tissue samples. These iPSCs retain ability to differentiate into every human cell type. Advances in differentiation and organogenesis move cellular in vitro modeling to a multicellular model capable of recapitulating physiology and disease. Here, we discuss limitations of traditional animal and tissue culture models, as well as the application of iPSC models. We highlight various techniques, including reprogramming strategies, directed differentiation, tissue engineering, organoid developments, and genome editing. We extensively summarize current established iPSC disease models that utilize these techniques. Confluence of these technologies will advance our understanding of pediatric diseases and help usher in new personalized therapies for patients.
疾病病理生理学的研究长期依赖于模型系统，包括动物模型和培养细胞。2006 年，Shinya Yamanaka 通过将体细胞重编程为诱导多能干细胞（iPSCs）取得了突破。这一革命性的发现为疾病建模和治疗干预提供了新的机会。有了既定的方案，研究人员可以从患者的血液、尿液和组织样本中生成 iPSC 系。这些 iPSCs 保留了分化为每一种人类细胞类型的能力。分化和器官发生的进步将细胞体外建模推进到能够重现生理和疾病的多细胞模型。在这里，我们讨论了传统的动物和组织培养模型的局限性，以及 iPSC 模型的应用。我们重点介绍了各种技术，包括重编程策略、定向分化、组织工程、类器官开发和基因组编辑。我们广泛总结了利用这些技术的当前已建立的 iPSC 疾病模型。这些技术的融合将增进我们对儿科疾病的理解，并有助于为患者带来新的个性化治疗方法。
