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Stem cells on path to rebuild blood ‘pipeline’

JOHNS HOPKINS (US) — Engineers can now prod stem cells to help build vein and artery networks, overcoming a stumbling block to growing replacement blood vessels in the laboratory.

New blood vessel networks, assembled in the lab for transplant into patients, would be a boon to people with circulatory systems damaged by heart disease, diabetes, or other illnesses.

“That’s our long-term goal: to give doctors a new tool to treat patients who have problems in the pipelines that carry blood through their bodies,” says Sharon Gerecht, assistant professor of chemical and biomolecular engineering at Johns Hopkins University. “Finding out how to steer these stem cells into becoming critical building blocks to make these blood vessel networks is an important step.”

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Gerecht and colleagues focused on turning stem cells, which can transform into various cell types needed around the body, into vascular smooth muscle cells. They describe the process in an article for the January print edition of Cardiovascular Research, published in advance in the journal’s online edition.

Two types have been identified: synthetic smooth muscle cells, which migrate through the surrounding tissue, continue to divide, and help support newly formed blood vessels; and contractile smooth muscles cells, which remain in place, stabilize the growth of new blood vessels, and help them maintain proper blood pressure.

To produce these smooth muscle cells, Gerecht’s lab has been experimenting with both National Institutes of Health-approved human embryonic stem cells and induced pluripotent stem cells. The latter are adult cells genetically reprogrammed to act like embryonic stem cells.

In an earlier study, Gerecht’s team was able to coax stem cells to become tissue that resembled smooth muscle cells but didn’t quite behave properly. In the new experiments, the researchers tried adding various concentrations of growth factor and serum to the previous cells. Growth factor is the “food” that the cells consume; serum is a liquid component that contains blood cells.

“When we added more of the growth factor and serum, the stem cells turned into synthetic smooth muscle cells,” Gerecht says. “When we provided a much smaller amount of these materials, they became contractile smooth muscles cells.”

This ability to control the type of smooth muscle cells formed in the lab could be critical in developing new blood vessel networks, she says.

“When we’re building a pipeline to carry blood, you need the contractile cells to provide structure and stability,” she says. “But in working with very small blood vessels, the migrating synthetic cells can be more useful.

“We still have a lot more research to do before we can build complete new blood vessel networks in the lab, but our progress in controlling the fate of these stem cells appears to be a big step in the right direction.”

The results may also help researchers better understand how new blood vessels form to nourish growing cancer tumors. That knowledge could be useful in devising cancer treatments.

Gerecht is affiliated with Johns Hopkins’ Institute for NanoBioTechnolgy and its Engineering in Oncology Center. The lead author of the paper is Maureen Wanjare, a doctoral student in Gerecht’s lab. Gerecht and undergraduate Frederick Kuo are co-authors.

A National Science Foundation Integrative Graduate Education and Research Traineeship, the National Institutes of Health, and the American Heart Association provided funding for the research.

Source: Johns Hopkins University

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