Mini-reviewOrganoids: An intermediate modeling platform in precision oncology
Introduction
Cancer causes a significant number of deaths worldwide. Although the last two decades have witnessed a 25% decline in cancer death rates that is equivalent to 2.1 million survivors [1], the absolute number of US annual cancer incidence and related deaths is projected to increase by 2030 [2]. Surgery, chemotherapy, and radiotherapy are routinely used to treat cancer together with immunotherapy and targeted therapy. However, they are not effective enough. Inter-patient heterogeneity varies the curative effects from person to person [3]. Researches use cell lines and patient-derived tumor xenografts (PDTXs) to study tumorigenesis. However, these methods have limitations. Genetic drifts and two-dimensional (2D) vision make the findings of cell lines unrealistic and unreliable; meanwhile, using PDTXs is expensive and time-consuming (Fig. 1a) [4]. These obstacles thus help drive the development of tumor organoids, which can recapitulate tumor biology relatively accurately.
Not until the recent decade did this three-dimensional (3D) in vitro culture technology stage a comeback (Fig. 2). Nowadays, organoid techniques provide unique platforms to model organ or tissue development and human diseases. Organoids are derived from pluripotent stem cells (PSCs) and organ-restricted adult stem cells (ASCs); the former is composed of pluripotent embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) [5]. Organoids can also be generated from established cell lines and transformed into PDTXs (Fig. 1b) [4].
Derived from patients, organoids are crucial tools for disease modeling, including cancer, cystic fibrosis (CF), and Zika virus [6]; neurodevelopmental disorders [7], [8], [9], [10]; liver disorders [11]; and drug testing [12], [13]; moreover, they can be stored as “living biobanks” (Fig. 1c) [14], [15]. Recently, the success of applying the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system to correct the CFTR locus made treating future CF patients possible [16]; meanwhile, established tumor-derived organoid cultures can be used for high-throughput drug screening [14]. These findings pave the way for the development of precision medicine. In this review, we mainly focus on organoids as a technology platform for cancer precision medicine, especially with potential translational applications for disease modeling, drug screening, and chemosensitivity studies.
Section snippets
Resources and methods
Methods for developing 3D organoids were based from earlier 2D culture systems and have improvements. Briefly, tumor cells isolated from tumor samples or PSCs/ASCs are embedded in serum-free media with growth factors to form organoids [17], [18]. The introduction of components, including growth factor-optimized media and basement membrane matrix (Matrigel), gives organoids the ability to self-renew and differentiate. Though different laboratories have their own preferences, Matrigel and
Advantages and limitations vs cell lines and PDTXs
As mentioned before, unlike traditional in vitro 2D cultures, organoids are similar to original tissues in their genetic composition and cellular architecture, harboring small populations of genetically stable, self-renewing stem-like cells that can give rise to fully differentiated progeny, comprising major cell lineages at frequencies similar to those in living tissue [73].
Cell lines have been a widely-used model for cellular studies for a long time. They are easy to culture and beneficial
Outlook and conclusions
Three-dimensional organoids are becoming popular and significant in tumor research and precision medicine. Three-dimensional bioprinting of multiple 3D organoids can be connected with a vascular network to develop an “organ-on-a-chip”, which may lead to advancements in toxicology. It enables us to observe pharmacokinetics and pharmacodynamics [70].
Transplantation of engineered patient-derived organoids will be potentially applied in regenerative medicine, but how to prepare their
Conflicts of interest
The authors declare that they have no competing interests.
Acknowledgements
We apologize to those colleagues whose important work could not be cited due to space constraints. This work was in part supported by the National Key Research and Development Program of China (No. 2017FYA0205300), the National Natural Science Foundation of China (No. 81702944, 81272801), Special Presidential Foundation of General Hospital of Jinan Military Command (No.2016BS04) and Shanghai Jiao Tong University Med-X Fund (No.YG2015MS20).
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These authors contributed equally to this work.