A high-throughput andautomated organoid platform developed by Tsinghua-Berkeley Shenzhen Institute(TBSI) researchers could speed up and address challenges in organoidproduction.
The breakthrough wasrecently published in the journal CellReports Medicine entitled “An Automated Organoid Platform withInter-organoid Homogeneity and Inter-patient Heterogeneity” by the Shaohua Ma &Laiqiang Huang research team at the Precision Medicine and Healthcare ResearchCenter, TBSI.
Organoid is an in vitro three-dimensional (3D) cellculture technology that captures and stably passes down the genomic andphenotypic profiles of human healthy organs and tumors. They arescalable, easy-to-culture, and may evaluate patient tumorsensitivity to anticancer drugs. However, current organoid technologies arelimited by significant variability,labor-intensive techniques, long culturing times, and tumor organoids inparticular face the challenge of maintaining intra-tumor and inter-patientheterogeneity.
The paper presented an automated organoid platform that generatesuniform organoid precursors in high-throughput. This is achieved bytemplating from monodisperse Matrigel droplets and sequentially delivering theminto wells using a synchronized microfluidic droplet printer. Each dropletencapsulates a certain number of cells (e.g. 1500 cells) which statisticallyrepresent the heterogeneous cell population in a tumor section. Thesystem produces > 400-μm organoids within 1 week (as opposed to 4-6 weeks ofculturing time) with both inter-organoid homogeneity and inter-patientheterogeneity. Usingthis technology platform, the team has successfully produced organoids fromvarious healthy tissues and tumors of mouse and human organs.
Figure 1. The automated organoid platform
To assess whether theorganoids resembled characteristics of theirparental healthy tissues and tumors, histological analysis was carried out. Resultsshowed that mouse organoids derived from lung, kidney and liver displayed similarhistology to the original cell, with significant recapitulation of epithelialorganization. Contrarily, human tumor organoids displayed much reducedepithelium in volume. In terms of gene expression, tumor-derived organoids werefound to have a highly overlapped (over 97%) single nucleotide variants (SNV)profile with their parental tumor tissue.
Figure 2. Histopathological characterization and gene expressionprofiling of healthy and tumor organoids.
The team also assessedthe potential of the organoids in evaluating different drug responses. Therapeuticprofiling on an anticancer drug library with 29chemotherapeutic drugs and 2 targeted drugs, rituximab and cetuximab, showed 80% accuracy in 21 patients.
Figure 3. Tumororganoids capture inter-patient heterogeneous responses to anticancer drugs.
Capable of creating multi-organ, cross-species, healthyand cancerous organoids in high throughput, high uniformity and reduced manualmanipulation, the developed platformis expected to play increasing roles in personalized cancer medicine, andtheranostics innovation for new drug development, and regenerative medicine.
For this article,TBSI Professor Laiqiang Huang and Associate Professor Shaohua Ma are thecorresponding authors, and their respective TBSI Ph.D. students Shengwei Jiangand Haoran Zhao are the first authors.
Link to the article: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(20)30208-1
