Making stem cells feel like they are growing in the right neighborhood may be key to success

An adage in real estate says that the most important thing is neighborhood, neighborhood, neighborhood. Researchers are learning that the same may be true for stem cell therapies. If you want to mature stem cells into the right adult tissue and get them to behave the way you want, you better pay attention to the environment where they are grown in the lab—before they are transplanted into people.

Two journal articles posted online this month provide good reasons to head the realtors’ advice. CIRM-grantee Shyni Varghese at the University of California, San Diego, provides an elegantly simple example. When trying to turn embryonic stem cells into bone researchers often embed them inside a hydrogel scaffold. This helps them to stay put when transplanted. But researcjers generally rely on chemical or genetic signals to get the stem cells to mature into bone. This results in a mixed population of bone cells and fat cells because both those cell types branch from the same maturation pathway.

Varghese’s team altered the scaffold to make it seem more like the neighboring bone cells the maturing stem cells would encounter in normal bone. They mineralized it with calcium and phosphate. And when they did, they got pure bone cells in the lab dish. What’s more, when they implanted those “tissues” into animals, they formed densely calcified bone—the hard kind we want. The team published the work in the Journal of Materials Chemistry online July 4.

A review article in the journal BioResearch provided a good overview of ways various groups have tried to precondition stem cells in the lab so that they will survive after transplant. One of the biggest stumbling blocks in the field remains the difficulty of getting stem cells to survive in the patient, whether those are humans or little mouse patients. It turns out from the research cited in this review that turning the lab growth environment into something more closely resembling the environment in the patient improves survival.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

They looked at several aspects of typical lab cell cultures that don’t mimic real tissue. Sites of injury where stem cells are needed often are also sites of lowered oxygen levels, inflammation and a disruption of the normal cell-to-cell contact that helps guides cell behavior. They found that adjusting each of those in the lab resulted in cells that were more likely to survive after transplant.

Most notably, when they grew cells in aggregates that restored cell-to-cell contact—restored the sense of neighborhood—cell survival improved significantly. Genetic Engineering & Biotechnology News wrote a brief summary of the work.

Don Gibbons

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