Stem cells have an unresolved potential for treating disease. One problem is that the cells must mature from the early fetal stage so they correspond to those in developed organs. New research – contradicting theories and textbooks – shows that specialized cells in fetal organs are not the only cells that can become stem cells. Under the right conditions, every cell can become a stem cell. This new knowledge simplifies the researchers’ task of finding a formula for developing the cells.
What started out as a simple controlled experiment in the laboratory ended up requiring more than 5 years of hard work. Nevertheless, the results, which have recently been published in one of the world’s leading journals, will require a comprehensive reformulation of the science textbooks used at universities. In addition, the results redefine the stem cell researcher’s task of producing mature stem cells for such purposes as transplantation and therapy.
“Previously, the question was both which and how, but our new results show that we can now focus on how to induce cells to become exactly the type of stem cells we need. In addition, our study indicates that the body is able to use this: for example, in connection with severe injuries. This creates a new and unique starting-point for developing stem cell therapies and helping people who have injuries in the intestinal epithelium,” explains Kim Jensen, Associate Professor, Biotech Research & Innovation Centre, University of Copenhagen.
The researchers made this surprising discovery during their quest to understand how the fate of stem cells is organized in the intestine. Postdoctoral fellow Jordi Guiu tried to develop a method for following the fate of an individual cell in the intestine. He introduced fluorescent proteins into the intestinal cells to monitor the fate of an individual cell through many cell divisions by means of advanced microscopy.
We were very surprised, because the literature stated that whether a cell could become a stem cell was predetermined. However, it turns out that all cells have the same ability to differentiate into a stem cell in the developed organ. This means that all cells in the fetal intestine can become stem cells if they receive the right signals.
Since the researchers could only explain a fraction of the intestinal growth from the cells previously thought to be fetal stem cells after their initial experiment, they collaborated with mathematics experts at the University of Cambridge. When they examined the data more closely, they surprisingly concluded that all cells in the intestine are equally able to develop into stem cells.
To further test the surprising plasticity of the cells, we used a 3D culture system and transplanted the cells into mice. This confirmed our conclusion that all cells can become stem cells under the right conditions.
Reducing the challenges of stem cell therapy
The researchers observed another very interesting phenomenon about stem cells when they examined injured tissue in the intestinal epithelium (lining). In this situation, the body apparently induces cells in the immediate vicinity to transition into the primitive state that characterizes the cells in the fetal state.
It is as if the cells are reset and lose some of the characteristics they have acquired in the developed organ. Since we have found that many cells in addition to stem cells can participate in repairing tissue following injury, we are basing our work on the hypothesis that this is caused by fetal reprogramming.
Only a few treatment options currently use stem cells, and these stem cells are isolated from developed organs. One major challenge has been to find the fetal stem cells that are responsible for developing the organs.
We can still only say with certainty that cells in the gastrointestinal tract have these characteristics. However, unpublished results indicate that this phenomenon is more common. In fact, we believe this is a general phenomenon throughout fetal development and for all cells.
If this turns out to be the case, it will reduce the challenges of stem cell therapy and repairing organs using stem cells from, for example, early fetuses.
“Alternatively, greater insight into the mechanisms by which the cells in the immature intestine mature to become stem cells could be used to better treat wounds that do not heal: for example, in the intestine.”
The European Research Council, the H2020 research programme, Lundbeck foundation, Novo Nordisk Foundation, Carlsberg Foundation and the Marie Curie Fellowship programme and others supported this project. “Tracing the origin of adult intestinal stem cells” has been published in Nature by authors at BRIC and the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen.