Difficulties in growing stem cells stymie research. Consistent conditions for growing stem cells will mean that more informative experiments can be performed in less time, and also that experiments done by scientists in different laboratories can be compared more easily.
Growing or “culturing” stem cells is difficult, largely because no one knows exactly what nutrients the cells need. All recipes for growing stem cells include a suite of proteins. These large, complex molecules are made by and purified from cultures of other cells. Other nutrients come from serum, a blood extract that is added to stem cells. Still more components are produced by other cells that grow in the same dish with the stem cells. These “feeder cells” are typically fibroblasts, the most common cells in connective tissue like cartilage and ligaments.
The first techniques reported for culturing human embryonic stem cells grew them over a layer of mouse fibroblasts bathed in calf serum. That was in 1998. Since then, researchers have figured out how to grow cells without serum and feeder layers, but they are still trying to work out exactly what nutrients embryonic stem cells need and how necessary nutrients vary under different conditions and with different cell types.
Researchers worry that contaminants from animals would mean that cells derived from embryonic stem cells could not be transplanted safely into humans. The cells could carry viruses or pathogens. Some researchers believe that human cells that have grown for years without animal products are free of harmful contaminants. Others favor human embryonic stem cells that have never been grown with animal components. However, these cells are not eligible for U.S. federal funding because they were created after August 2001, when President Bush declared that any embryonic stem cell lines created after that date would be ineligible for federal funding.
Human stem cell lines have been created and grown in a nutrient broth whose ingredients were highly defined and contained no animal products 2006,. However, both lines had chromosomal abnormalities, leaving researchers still unsure exactly what should be included in the recipe and why.
One reason why culturing human stem cells (both embryonic and adult) has been difficult is that research from other animals doesn't always apply to humans. For example, proteins that keep mouse embryonic stem cells from differentiating actually do the opposite to human embryonic stem cells, prompting them to differentiate into specialized cell types. However, human stem cells can be difficult to obtain and manipulate; experiments on human embryonic stem cells often require oversight by ethics boards and face funding restrictions, so new techniques tend to be developed first in mouse cells and then adapted to human ones.
Whether mouse or human, growing stem cells in culture is tricky. The proteins that stem cells need must be processed and stored carefully. Even then, the proteins vary from batch to batch. That makes testing different recipes difficult. And even getting all the right ingredients is not enough. Stem cells also need the right physical environment to grow. They must be attached to something, a complex web of support materials that scientists call the extracellular matrix. Human stem cells also seem to need close attachment to each other to survive and thrive.
Like avante garde architects designing new homes, tissue engineers are experimenting with scaffolding that prompt stem cells to proliferate and differentiate, or not, depending on the goal.
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Are stem cells hard to grow?. Nat Rep Stem Cells (2007). https://doi.org/10.1038/stemcells.2007.22