Stem Cells Harvested From Human Gut For First Time
Researchers from the University of North Carolina (UNC) at Chapel Hill, and other colleagues, report their findings in the 4 April online issue of Stem Cells.
In their background information they explain that while important facts about stem cells have been uncovered using stem cells from mice, to find information that is clinically useful, you eventually have to work with actual human stem cells.
A UNC press release describes the finding as a "leap forward" in stem cell research.
Senior author Scott T. Magness, assistant professor in the departments of medicine, biomedical engineering, and cell and molecular physiology at UNC, says:
"Not having these cells to study has been a significant roadblock to research. Until now, we have not had the technology to isolate and study these stem cells - now we have to tools to start solving many of these problems."
Magness and his team were the first US lab to isolate and grow single gut stem cells from mice, so they already had a head start in trying to pursue a similar approach in human gut tissue.
Also, thanks to the nearby gastric bypass surgery unit at UNC, they had ready access to sections of otherwise-discarded human intestinal tissue.
Their starting point was the technique they developed to isolate stem cells from mouse gut.
The first step was to establish that the differentiation genes CD24 and CD44 were expressed on the surfaces of human gut stem cells as they are on the mouse ones. This "basic cell surface signature" can then be a useful way to identify these particular groups of stem cells.
Then, by attaching fluorescent tags to these molecules, they were able to identify and isolate the stem cells from the human gut samples using a special cell-sorting device that is activated by fluorescence.
Not only were the researchers able to harvest the stem cells from the human gut samples, they were also able to separate them into two types: "active" and "reserve" (also called "facultative"), which is important for research, as they note in their study report:
"This study demonstrates that the cluster of differentiation genes CD24 and CD44 are differentially expressed across LGR5 positive 'active' stem cells as well as HOPX positive 'facultative' stem cells. Fluorescence-activated cell sorting enables differential enrichment of LGR5 cells (CD24 -/CD44+) and HOPX (CD24+/CD44+) cells for gene expression analysis and culture."
Researchers are very interested in investigating these separate stem cell types in order to discover how reserve stem cells cycle in order to replenish active stem cells damaged through chemotherapy, radiation therapy or other injury.
The authors conclude that their study provides "the fundamental methodology and basic cell surface signature necessary for isolating and studying intestinal stem cell populations in human physiology and disease".
Magness says now that they have shown it is possible to do this, the next step is to find out more about these stem cells and assess their potential, for instance:
"Can we expand these cells outside of the body to potentially provide a cell source for therapy? Can we use these for tissue engineering? Or to take it to the extreme, can we genetically modify these cells to cure inborn genetic disorders or inflammatory bowel disease?"
Funds from UNC's North Carolina Translational and Clinical Sciences Institute (NC TraCS) helped pay for the study.
Earlier this year, also for the first time, researchers in Japan showed it is possible to make cancer-specific immune system cells from induced pluripotent stem cells (iPSCs), bringing closer the day when therapies use cloned versions of patients' own cells to boost their immune system's natural ability to kill cancer cells.
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"CD24 and CD44 Mark Human Intestinal Epithelial Cell Populations with Characteristics of Active and Facultative Stem Cells";
Adam D. Gracz, Megan K. Fuller, Fengchao Wang, Linheng Li, Matthias Stelzner, James C.Y. Dunn, Martin G. Martin, Scott T. Magness; Stem
Cells published online 4 April 2013; DOI: 10.1002/stem.1391; Link to Abstract.
Additional source: University of North Carolina Health Care.
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