5 August 2021

Absence of stem cells in pancreas changes view on pancreatic cancer

Bianca-Olivia Nita

Bianca-Olivia Nita

New research by Oncode Investigator Louis Vermeulen and co-investigator Maarten Bijlsma shows that there are no stem cells in the pancreas. These unexpected findings potentially have major implications for pancreatic cancer research, since stem cells are often at the root of tumor development. This research was published today in the leading journal Cell Stem Cell.

In many organs, stem cells are responsible for the continued renewal of tissue. From these stem cells, all of the cell types that are necessary for a properly functioning organ are created. "We know, for example, that new tissue is continuously created in the intestine and that this process always starts in stem cells that are nested within the intestine," Louis Vermeulen explains. "This process is essential for keeping the organ healthy, but it is also often at the root of the development of cancer." Until now, it was unclear how this process worked in the pancreas, but Vermeulen and Bijlsma's research is changing that. "To our surprise, we saw in our experimental mouse models that all cells in the pancreas have the ability to repair the organ. Knowing that this is not strictly regulated from a small amount of stem cells changes our basic understanding of the biology of the pancreas and of the development of pancreatic cancer."

Patience is key

The original goal of the experiments, conducted by PhD students Sophie Lodestijn and Tom van den Bosch, was to gain more insight into the dynamics of stem cells in the pancreas. Ultimately finding no evidence for the existence of stem cells in the pancreas at all, was a scenario they had not initially anticipated. In order to answer their initial research question, they used a mouse model that has previously been used to investigate stem cells in the gut. "We knew in advance that this experiment would require a lot of patience," says co-PI Maarten Bijlsma. "This is because, compared to the intestines, the rate of tissue renewal in the pancreas is much slower. The strength of our model is that a fluorescent protein is spontaneously activated in random cells. As a result, we can do our experiments without exposing the animals to treatments that often affect the pancreas. This means that we can use microscopic recordings to precisely map what happens to these cells under normal conditions."

Obtaining the results therefore took several years. "After careful analysis and mathematical modeling, we were surprised to find no evidence for the existence of stem cells in the pancreas. In fact, our findings indicate that all cells that make digestive enzymes in the pancreas have so-called regenerative capacities." About 90% of the pancreas consists of these cell types that are responsible for, among other things, the production of digestive enzymes. These cells are also at the root of pancreatic canc

A microscopic recording of the pancreas (red) in which spontaneous activation of a fluorescent protein (yellow) allows the growth of tissue to be monitored.

Implications for pancreatic cancer research

Pancreatic cancer is one of the cancers for which the prognosis for patients remains poor: more than 3,000 people in the Netherlands die from pancreatic cancer every year. Thus, this new fundamental understanding of the biology of the pancreas comes at just the right time. "On average, almost 90% of people who receive this diagnosis die within a few years," Vermeulen says. A lot of research is being done worldwide to find new treatments for pancreatic cancer. "Groundbreaking innovation in drug research often comes from fundamental knowledge. We hope that our basic research will create new directions and thus provide a starting point for finding new treatments against pancreatic cancer." A first follow-up step comes from additional research by Vermeulen and Bijlsma themselves. In a new study, they demonstrate in a similar way that stem cells are absent in human pancreatic cancer. In addition, the researchers will use their mouse model to map out how regeneration works for other organs. Experiments looking at the skin, stomach and esophagus are now in progress.

The research published today was financially supported by Oncode Institute, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), The New York Stem Cell Foundation, and grants from KWF, the Gastrointestinal Foundation, the European Research Council and NWO.

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