Pancreatic organoids from stem cells

Organoids are artificial mini-organs that are designed to replicate the biological function of natural organs. They already exist for the liver, kidney, brain and intestine. After years of work, researchers from Ulm have succeeded in producing organoids of the three relevant cell types of the pancreas. These include the endocrine cells, which are responsible for the production and secretion of the blood sugar-regulating hormones insulin and glucagon in the pancreas. On the other hand, they were also able to differentiate the same pancreatic progenitor cells into cells with so-called exocrine function. These include in particular the so-called acinar cells, which are responsible for the production and secretion of digestive substances in the pancreas. „Until now, there were no reliable methods to produce acinar cells at all, let alone to produce them simultaneously from the same precursor cells as the other two cell types“, emphasises Professor Alexander Kleger, Director of the Institute of Molecular Oncology and Stem Cell Biology at Ulm University Hospital, who led the study. The Ulm researcher was recently honoured by the German Cancer Society with the prestigious German Cancer Award for Experimental Research.

The Ulm research team, in which other scientists from the University Hospital and the University of Ulm were also involved, has achieved something that was previously not possible: modelling the embryonic development of the pancreas in an in vitro system. A model was developed for this purpose that could reveal new fundamental findings in both diabetes and cancer research. By specifically switching on and off signalling pathways that play a role in pancreatic development, we can gradually mimic the stages of embryonic development in cell culture in order to grow the respective cell types of the pancreas," says Sarah Merz, first author of the study and research associate at Kleger's institute.

From the precursor population, endocrine, ductal and acinar cells

Pancreatic precursor cells were obtained from human pluripotent stem cells to generate the various pancreatic cell types. This precursor population is defined by a high expression of the marker glycoprotein 2 (GP2). Due to the specific GP2 enrichment, these precursor cells have the ability to develop simultaneously into three different cell lineages of the pancreas: endocrine, ductal and acinar cells. GP2 enrichment has made it possible for the first time ever to obtain acinar cells from a common precursor population.

„With this model, which includes all three cell lines of the pancreas, the effects of mutations can be investigated on a cell type-specific basis,

says Kleger. This brings major advantages for research into pancreatic tumours. Since 98 per cent of all pancreatic carcinomas affect the exocrine part of the pancreas, it is all the more important to be able to use model organoids in research that also include exocrine cells. In ductal adenocarcinoma, which is feared due to its high mortality rate, the glandular tissue is particularly affected. This human organ model could potentially also help to further reduce animal experiments in diabetes and pancreatic research in the future.

Publication note:

Single-cell profiling of GP2-enriched pancreatic progenitors to simultaneously create acinar, ductal and endocrine organoids. Sarah Merz, Markus Breunig, Michael Karl Melzer, Sandra Heller, Sandra Wiedenmann, Thomas Seufferlein, Matthias Meier, Jana Krüger, Medhanie A Mulaw, Meike Hohwieler, Alexander Kleger. In: Theranostics 2023, Vol. 13, Issue 6, doi: 10.7150/thno.78323

Further information:

Prof. Dr Alexander Kleger, Director of the Institute of Molecular Oncology and Stem Cell Biology at Ulm University Hospital and Head of the Interdisciplinary Pancreatology Section, Department of Internal Medicine I, Ulm University Hospital

Current announcement of the "Medical Faculty of the University of Ulm" from 11 April 2023