by Cindy A. Abole, Public Relations

As astronaut John Glenn and his colleagues aboard Discovery begin analyzing experiments they performed in high Earth orbit, scientists like MUSC's Adam Smolka, Ph.D., are making important strides in NASA-funded, ground-based biotechnology research aimed at better understanding how cells function and assemble into tissues.

An associate professor of medicine and cell biology in the Department of Medicine's Gastroenterology and Hepatology Division, Smolka sought and won funding from NASA's Microgravity Biotechnology Program in 1997. His study addresses the effects of simulated microgravity on isolated gastric cells, particularly their ability to reform functional mucosa and their defensive response to the ulcer-causing bacterium Helicobacter pylori. This work complements Smolka's long-term NIH-funded studies of gastric secretory physiology.

Today, space biotechnology plays an increasingly important role in medical research, pharmaceutical drug development, agricultural research and environmental protection. Managed by NASA's Johnson Space Center, the Microgravity Biotechnology Program involves more than 100 scientists and engineers. It contributes to three areas of research: fundamentals of biotechnology, protein crystallography, and cell science.

“Cells lining the stomach form tubular glands which secrete highly corrosive hydrochloric acid needed to sterilize ingested food,” Smolka said. “At a fundamental level, knowing how cell membranes pump ions to extraordinary concentrations is a challenge. More practically, understanding the molecular mechanisms of acid secretion is central to effective clinical management of ulcers. Also, with the realization that H. pylori causes ulcers and gastric cancers, molecular details of the bacterium's assault on gastric cells have become essential.”

Through the years, studies of isolated gastric cells and their constituents have yielded important insights, but difficulties in establishing and propagating gastric cells in laboratory culture have always posed a barrier. Cells cultured in petri dishes are pulled to the bottom by gravity, where they form flat, two-dimensional monolayers, quite unlike the three-dimensional glandular assemblies found in an intact, functional stomach. Constraints on feeding the cells and removing waste products further limit the usefulness of Earth cultures.

In the weightlessness of space, however, cells remain suspended and motionless in their culture medium. Smolka hypothesizes that dense microgravity cultures of gastric cells, under minimal shear stress and guided by inter-cellular signals, will reassemble into functional tissue. Such an organoid would be an invaluable model for gastric secretory studies. For now, Smolka focuses on growth proliferation of gastric cells in NASA-developed bioreactors which simulate microgravity. This work has already yielded a design for improved nutrient and gas perfusion of microgravity bioreactors. Related studies with gastric adenocarcinoma cells address mechanisms of acid pump gene expression, and whether a gastric cell's response to infection by H. pylori may be affected by gravity.

“After all,” Smolka said, “life evolved in Earth's gravitational field. Do cells possess a gravitational sensor? Does altering the gravitational vector alter patterns of gene expression? These questions may be answered as we move into orbital space. Meanwhile, we have observed that simulated microgravity generated in our ground-based NASA bioreactors dramatically increases the pro-inflammatory response of gastric cells infected with H. pylori. Whether this result points to a gravitational sensor or to improved cell culture remains to be seen. But in either case, cell science advances.”