Organoids from the Human Fetal and Adult Pancreas

Abstract

Purpose of ReviewNovel 3D organoid culture techniques have enabled long-term expansion of pancreatic tissue. This review comprehensively summarizes and evaluates the applications of primary tissue–derived pancreatic organoids in regenerative studies, disease modelling, and personalized medicine.Recent FindingsOrganoids derived from human fetal and adult pancreatic tissue have been used to study pancreas development and repair. Generated adult human pancreatic organoids harbor the capacity for clonal expansion and endocrine cell formation. In addition, organoids have been generated from human pancreatic ductal adenocarcinoma in order to study tumor behavior and assess drug responses.SummaryPancreatic organoids constitute an important translational bridge between in vitro and in vivo models, enhancing our understanding of pancreatic cell biology. Current applications for pancreatic organoid technology include studies on tissue regeneration, disease modelling, and drug screening.

Cell Lineage Infidelity in PDAC Progression and Therapy Resistance

“…Organoids can have clinical implications as they mimic patient response and can be used to identify patients that would benefit from certain treatments ( Tiriac et al, 2018 ). Additionally, organoids derived from embryonic pancreatic cells can also contribute to understanding better the human pancreatic development and lineage relationships, which are altered in PDAC ( Balak et al, 2019 ). Finally, organoid cultures can be established and propagated (albeit for a limited time) from adult pancreatic exocrine cells, which allows evaluating the contribution of individual genes and their influence on the PDAC tumorigenic process by the stepwise introduction of genetic alterations through genome editing approaches ( Figure 3B ) ( Greggio et al, 2013 ; Huch et al, 2013 ; Huch and Koo, 2015 ; Baker et al, 2016 ).…”

A pancreas tumor derived organoid study: from drug screen to precision medicine

“…Because PTOs can routinely be obtained from normal human epithelia, mutational processes during different phases of malignancy can be monitored in vitro, and in vitro culture of a range of premalignant pancreas neoplasias is now feasible [ 27 ]. However, PTOs do not rely on the R-spondin protein to activate Wnt pathway mutations, and their dependence on other niche growth factors is specifically lost in the adenoma-to-carcinoma transition [ 32 , 45 , 54 ]. Another relevant application of PTOs is their use in xenografts [ 55 , 56 ].…”

“…PTOs constitute a tool for rapid drug assessment of individual tumors before or in parallel to implementing treatment in patients with PDAC [ 92 , 93 ]. Although a one-week time period between biopsy and drug selection has been reported, more recent studies have suggested that extensive drug screening should be performed within 3–4 weeks post-biopsy [ 45 , 60 , 94 ]. This technique can potentially reveal individual treatment vulnerabilities according to the genetic mutation profile and therapeutic response in organoids or determine the next lines of therapy in case of ineffective first-line treatment [ 95 , 96 ].…”

“…Additionally, drug screening could be examined in combination with dynamic live imaging for obtaining functional optical metabolic findings [ 45 , 63 , 94 , 98 – 102 ] (Fig. 3 ).…”

3D Pancreatic Tissue Modeling in vitro: Advances and Prospects

“…Stem cell engineering has made it possible to develop functional β cell differentiation and representative 3D stem-cell-derived tissues, called organoids, to recreate critical functions of native pancreatic tissue in vitro [10][11][12][13][14][15][16][17][18] . Millman et al succeeded in generating stem-cell-derived β cells from diabetic patients, and they suggested that this approach might be an attractive candidate for patient-specific treatment, drug screening platform, and improvement of β cell biology 13 .…”