In many applications of organoid technology, improving model complexity to more closely resemble the native tissue is a major goal. Such is the case for pancreatic organoids, which so far have not recapitulated the full complement of cell types present in their human counterpart. In a paper now published in Cell, Andersson-Rolf et al. introduce an organoid model that more closely mimics the human pancreas in its fetal stage.

The authors generated human fetal pancreatic organoids (hfPOs) from fetal pancreas tissue of gestation weeks 14 to 16. The organoids contained the three main epithelial compartments —acinar, ductal and endocrine cells — and could be cultured long-term, for over 2 years. Characterization of hfPO cells showed that they had similar transcriptional profiles to human fetal pancreatic tissue and formed functional enzymes and hormones, mimicking the first-trimester stage of pancreatic development. Some acinar cells showed signs of further maturation, as indicated by the presence of dark zymogen granules in which digestive enzymes are stored.