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By Marla Vacek Broadfoot, PhD

The human gut is a remarkable thing. Every week the intestines regenerate a new lining, sloughing off the equivalent surface area of a studio apartment and refurbishing it with new cells. For decades, researchers have known that the party responsible for this extreme makeover were intestinal stem cells, but it wasnt until this year that Scott Magness, PhD, associate professor of medicine, cell biology and physiology, and biomedical engineering, figured out a way to isolate and grow thousands of these elusive cells in the laboratory at one time. This high throughput technological advance now promises to give scientists the ability to study stem cell biology and explore the origins of inflammatory bowel disease, intestinal cancers, and other gastrointestinal disorders.

But it didnt come easy.

One Step Forward . . .

When Magness and his team first began working with intestinal stem cells some years ago, they quickly found themselves behind the eight ball. Their first technique involved using a specific molecule or marker on the surface of stem cells to make sure they could distinguish stem cells from other intestinal cells. Then Magnesss team would fish out only the stem cells from intestinal tissues and grow the cells in Petri dishes. But there was a problem. Even though all of the isolated cells had the same stem cell marker, only one out of every 100 could self-renew and differentiate into specialized cells like a typical stem cell should. (Stem cells spawn cells that have specialized functions necessary for any organ to work properly.)

The question was: why didnt the 99 others behave like stem cells? Magness said. We thought it was probably because theyre not all the same, just like everybody named Judy doesnt look the same. There are all kinds of differences, and weve been presuming that these cells are all the same based on this one name, this one molecular marker. Thats been a problem. But the only way to solve it so we could study these cells was to look at intestinal stem cells at the single cell level, which had never been done before.

Magness is among a growing contingent of researchers who recognize that many of the biological processes underlying health and disease are driven by a tiny fraction of the 37 trillion cells that make up the human body. Individual cells can replenish aging tissues, develop drug resistance, and become vehicles for viral infections. And yet the effects of these singular actors are often missed in biological studies that focus on pooled populations of thousands of seemingly identical cells.

Distinguishing between the true intestinal stem cells and their cellular look-a-likes would require isolating tens of thousands of stem cells and tracking the behavior of each individual cell over time. But Magness had no idea how to accomplish that feat. Enter Nancy Allbritton, PhD, chair of the UNC/NCSU Joint Department of Biomedical Engineering. The two professors met one day to discuss Magness joining the biomedical engineering department as an adjunct faculty member. And they did discuss it. And Magness did join. But the meeting quickly turned into collaboration. One of Allbrittons areas of expertise is microfabrication the ability to squeeze large devices into very small footprints. During their meeting, Allbritton showed Magness her latest creation, a device smaller than a credit card dotted with 15,000 tiny wells for culturing cells.

See the original post here:
A Single-Cell Breakthrough