Isolation and in vitro cultivation turns cells from exocrine human pancreas into multipotent stem-cells

Several research groups have reported on the existence and in vitro characterization of multipotent stem-cells from the pancreas. However, the origin of these cells remains largely unexplained. Here, we report that in vitro culturing itself can turn adult cells from human exocrine pancreas into a cell population with typical stem cell characteristics. A simple, yet reliable method enabled us to track cell fates: Combining automated continuous observation using time-lapse microscopy with immunocytochemical analyses, we found that a significant fraction of the pancreatic cells (≈14%) can survive trypsination and displays a drastic change in the protein expression profile. After further cultivation, these cells give rise to a heterogeneous cell population with typical multipotent stem cell characteristics; i.e. they proliferate over long time periods and continuously give rise to specialized cells from at least two germ layers. Although we cannot exclude that a rare pre-existing stem cell-type also contributes to the final in vitro-population, the majority of cells must have been arisen from mature pancreatic cells. Our findings indicate that multipotent cells for regenerative medicine, instead of being laboriously isolated, can be generated in large amounts by in vitro de-differentiation.