Researchers are increasingly interested in curing debilitating intestinal diseases by using people’s own cells. A new protocol shows how this is done in mice.
Inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, are debilitating intestinal diseases in which the immune system is hyperactivated and the intestinal tissue is damaged.
Current treatments focus on reducing immune system activation and not repairing the damaged tissue. Based on experiments in mice, transplantation of people’s own cells may end up complementing current treatment options.
The great interest from the research community in transplanting cells into the colon has led researchers to publish a protocol describing how to optimally perform these experiments in mice.
“We hope that transplanting intestinal epithelial cells will complement existing therapies for patients with inflammatory bowel disease and thus help them better than we can today. However, this requires more research. The published protocol will assist researchers globally in carrying out the relevant studies in mice,” explains a researcher involved in developing the protocol, Kim Bak Jensen, Professor, Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, University of Copenhagen.
The protocol has been published in Nature Protocols.
Great interest in the protocol
In 2009, researchers in the Netherlands discovered that stem cells from the intestinal epithelium could be cultured in the laboratory in the presence of specific growth factors. The epithelium formed organoids, structures that maintain the functions associated with the intestine such as secretion of intestinal hormones and absorption of nutrients.
Since then, experiments in mice have shown that organoids can be used to repair a damaged colon. The method originally used on mice has now advanced so far that researchers in Japan are carrying out the first trials on people.
Experiments in mice are far from exhausted, however, and the researchers have therefore published a protocol: a step-by-step explanation of how to select the cells from the intestine, culture them and reinsert them into the colon. This will enable more researchers to obtain insight into how potentially to refine the method even further and also to address basic biological questions.
The principles outlined are also relevant for clinical trials. However, transitioning from experiments in mice to people requires a lot of optimisation and that the cells introduced into people essentially comply with the same requirements as any other type of medication.
“Our protocol has attracted great interest for many years, and researchers who want to know how we do it have contacted us countless times. Researchers can save 6–12 months of development efforts by using the tips and tricks that we have collected over the years. We therefore felt that publish the protocol would be a good idea,” says Kim Bak Jensen.
Tricks to help other researchers
The protocol is not that complicated, but Kim Bak Jensen highlights fluid therapy as one useful trick the researchers discovered in close collaboration with veterinarians in Denmark.
Like patients with ulcerative colitis suffering from bloody diarrhoea who receive fluid therapy, the researchers provide the experimental mice with fluid therapy. This significantly reduces the severity of the procedure for the animals, represents an excellent example for how collaborations between researchers and veterinarians can develop better disease models and provides much more reproducible data.
Another important point is inserting the cells into the intestine with a flexible catheter, which is also relevant for people with an intestinal disease.
“We have used knowledge from all our partners to optimise the method. The focus is not just understanding the animals’ biology but also understanding what parameters are important from a clinical perspective,” explains Kim Bak Jensen.
Collaborating with doctors in developing treatment
Kim Bak Jensen hopes that the protocol can provide even more impetus to this field.
About 30,000 people in Denmark have ulcerative colitis. The treatment options focus on the hyperactivated immune system and not as much on healing the intestinal mucosa. However, supporting mucosal healing and stopping the immune hyperactivation will be important.
As researchers advance their knowledge on how to use people’s own cells to repair damage, the two types of therapies will hopefully be complementary.
“A number of patients with inflammatory bowel disease go from one treatment to the next with limited change in the disease trajectory. We hope that we can help these people by providing them with complementary treatments. Specifically, we hope that we within reNEW in collaboration with our partners in Japan and the Department of Gastroenterology at Herlev & Gentofte Hospital will be able to push these findings towards clinical practice,” concludes Kim Bak Jensen.
