Disease Modeling and Therapeutics Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Int J Mol Sci. 2018 Mar 21;19(4):936. doi: 10.3390/ijms19040936.
The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host-microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.
人们对人类诱导多能干细胞(hiPSC)衍生类器官培养的兴趣日益浓厚,这源于对各种定向多谱系分化和形态发生过程的操纵,这些过程模拟了器官发生。类器官是由多种细胞类型组成的三维(3D)结构,通过自我组织来重现体外胚胎和组织发育。该模型在模拟功能、结构和体内所见组织的几何特征方面优于传统的二维(2D)细胞培养方法。
本综述旨在强调 3D 类器官技术在模拟复杂遗传性疾病、癌症、宿主-微生物相互作用以及在转化和个性化医学中的潜在应用方面的最新进展,在这些应用中,类器官培养物被用于通过高通量药物筛选发现早期疾病检测的诊断生物标志物。此外,本综述还旨在讨论利用类器官进行疾病建模的优缺点。
总之,使用 hiPSC 衍生的类器官研究人类疾病可能由于类器官中存在的结构和微环境的相似性更好地说明所涉及的过程,这也允许在体外适当重现药物反应。