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"Organoids—tiny, lab-grown 3D clusters of cells—are a useful tool for studying organ development, disease, and drug responses. These miniature organs-in-a-dish are powerful, but they’re not perfect: Recreating the complex interplay of different cell types found in full-sized organs remains tricky.
For example, most pancreatic organoids only contain a single cell type, which makes it difficult for researchers to fully understand how different cell types work together in a functioning pancreas. ...
at the Hubrecht Institute, set out to build a better pancreatic organoid, she decided to include all three main cell types found in this organ. She would have to figure out how to co-culture acinar cells, which produce digestive enzymes, ductal cells, which transport these enzymes, and endocrine cells, which regulate blood sugar levels by releasing hormones. ..."
From the highlights and abstract:
"Highlights
• Human fetal pancreatic organoids (hfPOs) established from 8 to 17 GWs expand long-term
• hfPOs recapitulate the epithelial complexity of human fetal pancreas
• hfPOs generate functional acinar and endocrine cell lineages upon differentiation
• LGR5 marks tripotent stem cells, precursors to all exocrine and endocrine lineages
Summary
The mammalian pancreas consists of three epithelial compartments: the acini and ducts of the exocrine pancreas and the endocrine islets of Langerhans. Murine studies indicate that these three compartments derive from a transient, common pancreatic progenitor.
Here, we report derivation of 18 human fetal pancreas organoid (hfPO) lines from gestational weeks 8–17 (8–17 GWs) fetal pancreas samples.
Four of these lines, derived from 15 to 16 GWs samples, generate acinar-, ductal-, and endocrine-lineage cells while expanding exponentially for >2 years under optimized culture conditions.
Single-cell RNA sequencing identifies rare LGR5+ cells in fetal pancreas and in hfPOs as the root of the developmental hierarchy. These LGR5+ cells share multiple markers with adult gastrointestinal tract stem cells.
Organoids derived from single LGR5+ organoid-derived cells recapitulate this tripotency in vitro. We describe a human fetal tripotent stem/progenitor cell capable of long-term expansion in vitro and of generating all three pancreatic cell lineages."
Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages (open access)
Graphical abstract
Figure 1 Establishment of hfPOs
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