Human Intestinal Stem Cell for Regenerative Medicine

For the very first time, researchers have accomplished the growth of human colon stem cells in a lab-plate thereby making a significant progress towards regenerative medicine. The ground-breaking research that is published in Nature Medicine has been conducted by researchers of the Colorectal Cancer Lab at the Institute for Research in Biomedicine (IRB Barcelona).

The inner layer of the large intestine is regenerated on a weekly basis by the stem cells of the colon throughout our life. Although scientists were aware of the existence of these cells for decades, their identity continued to be elusive. The specific localization of the stem cells in the human colon was discovered by a team of scientists led by the ICREA Professor and researcher at the Institute for Research in Biomedicine (IRB Barcelona) Eduard Batlle. They established a method to facilitate their isolation, and in-vitro culture and propagation in lab-plates.

In-vivo cell growth in a lab-plate necessitates the cells to be equipped with the right nutrient mix, growth factors, and hormones. But just like each of our body cells differ from one another, so do the optimal growth conditions in the lab. As a result, the lab culture of human adult stem cells has been an unattainable task, thus far.

The team also elucidated conditions for maintaining living human colon stem cells (CoSCs) in-vivo.

First author and IRB Barcelona researcher Peter Jung explains, “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.”
Ten years of intense research aimed at understanding the biology of the intestinal stem cells and its association with cancer has led to this achievement.
The research is a close collaborative achievement between a group led by Hans Clevers at the Hubretcht Institute and University Medical Center Utrecht in The Netherlands, and Batlle’s team María A. Blasco at the Spanish National Cancer Research Centre in Madrid (Spain).
Jung explained, “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.”

Scientific researchers have now established the technique of isolating CoSCs and deriving stable CoSCs lines, which can grow undifferentiated for months.

Jung says, “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. This achievement opens up an exciting new area of research with the potential to bring about a huge breakthrough in regenerative medicine.”

The concept of regenerative medicine revolves around growing new tissues and organs from patients’ cells in the lab.
Jung concludes, “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.”

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