New gene-editing system enables large-scale studies of gene function.
An MIT/NASA tissue-engineering experiment currently orbiting the Earth aboard the Russian space station Mir is the first of its kind and has now run longer than any other study of cells in space.
Previous space experiments involving cells focused on the cells themselves and lasted only about 10 days. The current experiment, which is aimed at growing full tissues, was launched to Mir on September 16 and will remain there for 150 days, when a shuttle will bring it down. The study features bovine cartilage cells growing on polymer scaffolds in a bioreactor the size of a coffee cup.
The goal of the experiment is to explore the effects of microgravity on tissue growth. Experiments on Earth under simulated microgravity have indicated that cells grow well in this environment, but "actual microgravity is an unknown. We don't know how it will affect tissue growth," said Lisa E. Freed, a research scientist at the Harvard-MIT Division of Health Sciences and Technology.
Dr. Freed and Gordana Vunjak-Novakovic, a research scientist at the Whitaker College of Health Sciences and Technology, led the 13-member MIT team involved in the work. Dr. Neal Pellis is head of the NASA team for the project, which includes some 15 scientists and engineers.
"The idea is to use this as a model system to study tissue growth in space," Dr. Freed said. Cartilage was the tissue selected because it is hardy and has been studied extensively in the laboratory. "If it works, the general system could be used to grow tissues that might be more relevant to the effects of microgravity on humans," she said.
For example, NASA is very interested in bone, since bones can become brittle in microgravity. If scientists could grow human bone tissue in space, they could conduct controlled experiments on the engineered tissue. This would substantially add to the data on this subject, complementing measurements obtained from astronauts themselves.
Drs. Freed and Vunjak-Novakovic have been working on cartilage tissue engineering for six and a half years in the laboratory of Robert S. Langer, Germeshausen Professor of Chemical and Biomedical Engineering. As a result, NASA approached them about two years ago about developing a tissue-engineering experiment for Mir.
"We had the model system that was of interest to them," said Dr. Vunjak-Novakovic, who is also an adjunct professor at Tufts University. The MIT system allows the regeneration of tissue with clinically useful dimensions, not just the growth of individual cells.
The system involves "seeding" porous polymer scaffolds with bovine cartilage cells. Ten cell-polymer constructs, each of which is about eight millimeters in diameter by four millimeters thick, are then put into the bioreactor. The bioreactor is an integral part of an automated cell-culture system that supplies the cells with nutrients and gases and removes wastes so that they can grow into a full tissue. The entire system is the size of a microwave oven.
"The cells first attach to the polymer scaffold, and then they secrete a matrix," said Dr. Freed, who noted that the cells make up only a small fraction of cartilage tissue (which is composed primarily of matrix). Over time, the pores of the scaffold are filled in with matrix, the scaffold biodegrades, and a full tissue is regenerated. "The main purpose of the scaffold is to give the tissue its shape at first," she explained.
To date, the cartilage cells in the system aboard Mir appear to be alive and growing. This is in spite of a six-week launch delay caused by mechanical problems with the shuttle's booster rockets and a series of hurricanes. There was also a tense situation early on when a faulty cable connection threatened the experiment. Thanks to teamwork between the ground support team and the astronauts on the shuttle and Mir, however, the cable problem was discovered and solved.
To check the status of the experiment, astronaut John Blaha takes weekly samples of the fluid surrounding the cell-polymer constructs (according to a NASA newsletter, the experiment is one of Mr. Blaha's favorites). For each sample Mr. Blaha measures parameters including pH and oxygen content. "Cell growth changes these parameters, so measuring them is a way of monitoring the experiment," Dr. Freed said.
She noted, however, that these measurements give "only broad clues as to how the experiment is going." The researchers won't be able to sample the actual cell-polymer constructs until the experiment is brought back to Earth.
The main purpose of the experiment is to see if the system has potential for studying tissue engineering in space. "Nothing even close to this has been done before with such a complex biotechnology system for such a long time," Dr. Freed said. "We would consider the experiment very successful if any of the tissue is alive at the end."
The work will also allow the researchers to compare tissue growth under actual microgravity with growth under simulated microgravity. In addition to the cartilage system on Mir, two parallel systems at the Johnson Space Center are running under simulated microgravity.
The whole experience has been quite exciting, Dr. Freed said. "It's really neat to walk outside and know that your experiment is up in the sky somewhere."
The work was funded by a NASA microgravity tissue engineering grant.
A version of this article appeared in MIT Tech Talk on October 23, 1996.