For the first time researchers of the Colorectal Cancer Lab at the Institute for Research and Biomedicine (IRB Barcelona) identified and managed to grow human colon stem cells in a lab-plate. The research, published in Nature Medicine is a major important advancement for regenerative medicine.
Stem cells of the colon regenerate the inner layer of our large intestine weekly throughout our lives and although researchers had evidence of their existence for decades, their identity has so far not been established.
Study leader ICREA Professor Eduard Batlle and his research team at the Institute for Research in Biomedicine (IRB Barcelona) discovered the exact localization of the stem cells in the human colon and developed a method of allowing them to isolate the cells and propagate them in lab-plates (in vitro expansion).
Human adult stem cell culture in labs has been a virtually impossible mission until now. In order to grow cells outside the body the lab-plates generally need to be provided with the correct mixture of nutrients, growth factors and hormones, but just as each of the more than 200 body cell types differs from each other, so too do optimal growing conditions in the lab.
Batlle's team also managed to establish the correct conditions to maintain living human colon stem cells (CoSCs) outside of the human body. IRB Barcelona researcher Peter Jung, joint first author of the study together with Toshiro Sato, from the University Medical Center in Utrecht in The Netherlands explained:
"This is the first time that it has been possible to grow single CoSCs in lab-plates and to derive human intestinal stem cell lines in defined conditions in a lab setting."
The development achieved its success after over 10 years of intense research into the characterization of the biology of the intestinal stem cells and its connection with cancer. The research was a joint collaboration of Batlle's team together with group leader Hans Clevers from the Hubretcht Institute and University Medical Center Utrecht in The Netherlands and María A. Blasco from the Spanish National Cancer Research Centre in Madrid.
Co-author Peter Jung explains:
"For years, scientists all over the world have been trying to grow intestinal tissue in lab-plates; testing different conditions; using different nutritive media. But because the vast majority of cells in this tissue are in a differentiated state in which they do not proliferate, they survived only for a few days. The aim of this study was to find a way to identify and select individual CoSCs and to grow them while maintaining their undifferentiated and proliferative state in lab conditions. Thus, we would be able to model how they grow - in number - and differentiate into normal intestinal epithelial cells in lab-plates.
The scientific community now has a defined 'recipe' for isolating CoSCs and deriving stable CoSCs lines, which have the capacity to grow undifferentiated for months. In fact, now we can maintain stem cells in a plate up to 5 months or we can induce these cells to differentiate artificially, as they do inside our bodies".
In a concluding statement Jung said:
"This achievement opens up an exciting new area of research with the potential to bring about a huge breakthrough in regenerative medicine. Regenerative medicine - or the idea of repairing the body by developing new tissues and organs as the old ones wear out - involves growing new cells from patients into tissues and organs in a lab. However, the main element for making regenerative medicine a reality, namely adult stem cells, are just starting to be understood.
Now that guidelines for growing and maintaining colon stem cells in the lab are in place, we have an ideal platform that could help the scientific community to determine the molecular bases of gastrointestinal cell proliferation and differentiation. It is also suspected that alterations in the biology of CoSCs are at origin of several diseases affecting the gastrointestinal tract, such as colorectal cancer or Crohn's disease, an autoimmune and inflammatory disorder. Our discovery also paves the way to start exploring this exciting field."
Written by Petra Rattue