Regenerating intestinal tissue by stem cells

16 June 2011

ZonMW (the Netherlands Organisation for Health Research and Development) has granted € 2 million for collaboration between the Wilhelmina Childrens Hospital (WKZ/UMC Utrecht) and the Hubrecht Institute. This collaboration will focus on regenerating intestinal tissue by stem cells. The program is integrated in the UMCU’s   focusgroup of Stem Cells & Regenerative Medicine.

There are many conditions affecting the epithelium of the small intestine. Replacement of the non-functional epithelium is currently not possible unless the entire organ is transplanted.  The pediatric genetic disorder “Microvillus Inclusion Disease” (MVID) is characterized by epithelial cells which cannot take up nutrition.  Treatment of children with MVID consists of the administration of total parental nutrition (TPN). This works well until no suitable veins are accessible and the patient requires whole organ transplantation. Because of the high mortality and morbidity of intestine transplantations only patients with serious complications of the TPN are considered for the transplantation. For this patient group and other patients with serious intestinal damage we will attempt to develop an alternative therapy.

The finding that all organs contain stem cells which have the potential to repair damage tissue, created the opportunity to use these cells for regenerative therapy. The central question of the project of the Hubrecht Institute and the WKZ is if we can safely and effectively transplant ex vivo expanded stem cells to restore intestinal function in patients.  

Recently we demonstrated that we can expand multipotent intestinal stem cells for an unlimited time. This technique will allow us to generate large quantities of epithelial cell to be used for transplantation. We have shown that we can indeed transplant mouse intestinal cells which were expanded back into a recipient mouse.

We will further optimize these protocols to develop a technique to use the stem cell cultures to restore intestinal epithelium in mouse models. These experiments in a mouse MVID model, will give us a proof of concept for the use in humans with MVID. If nutrition uptake is restored it will demonstrate the technique is ready for a clinical trials. If successful, this will also demonstrate that the therapy can be used on other patients with serious intestinal damage or other disorders.