Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery
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Human Female Reproductive System Organoids: Applications in Developmental Biology, Disease Modelling, and Drug Discovery Yutong Cui 1 & Huanqiang Zhao 1 & Suwen Wu 1 & Xiaotian Li 1,2,3 Accepted: 7 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Organoid technique has achieved significant progress in recent years, owing to the rapid development of the three-dimensional (3D) culture techniques in adult stem cells (ASCs) and pluripotent stem cells (PSCs) that are capable of self-renewal and induced differentiation. However, our understanding of human female reproductive system organoids is in its infancy. Recently, scientists have established self-organizing 3D organoids for human endometrium, fallopian tubes, oocyte, and trophoblasts by culturing stem cells with a cocktail of cytokines in a 3D scaffold. These organoids express multicellular biomarkers and show functional characteristics similar to those of their origin organs, which provide potential avenues to explore reproductive system development, disease modelling, and patient-specific therapy. Nevertheless, advanced culture methods, such as co-culture system, 3D bioprinting and organoid-on-a-chip technology, remain to be explored, and more efforts should be made for further elucidation of cell–cell crosstalk. This review describes the development and applications of human female reproductive system organoids. Keywords Disease modelling . 3D remodeling . Endometrium . Fallopian tube . Follicle . Organoids . Stem cell . Trophoblast
Introduction Organoids are extensions of two-dimensional (2D) biology that present as multicomponent aggregations with tissueautonomous self-organization involved in homeostasis, regeneration, and development [1, 2]. In recent years, organoid technique has been widely applied in multi-disciplinary research fields, on the basis of more advanced stem cell and three-dimensional (3D) culture skills. This thriving 3D technology provides a novel cell culture method, exhibiting more The first two authors should be regarded as joint first authors and contributed equally * Xiaotian Li [email protected] Yutong Cui [email protected] Huanqiang Zhao [email protected] 1
Obstetrics and Gynaecology Hospital of Fudan University, Shanghai, China
2
Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China
3
Institute of Biomedical Sciences, Fudan University, Shanghai, China
intuitive spatial structure that makes the exploration of physiological and pathological mechanisms more convenient. Combination of 3D culture skills and stem cells, including adult stem cells (ASCs) and pluripotent stem cells (PSCs), allows self-organized and self-renewing “organoids” present disease processes temporally. Organoids not only exhibit characteristics of traditional 2D cell culture, such as biomarkers and biofunctions, but also show multiple morphological components as well as realize multicellular interactions [1–5]. Up to date, organoids derived from the g
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