Physiological Systems Experiment 3/STS-57

PAYLOAD PROFILE: PSE.03/STS-57

Mission Duration: 10 days

Date: June 21–July 1, 1993

Life Science Research Objectives
• To study the role that growth factors play in tissue repair

Life Science Investigations
• Bone Physiology (PSE3-1, 2)

Organisms Studied
Rattus norvegicus (rat)

Flight Hardware
Ambient Temperature Recorder (ATR-4)
Animal Enclosure Module (AEM)
AEM Water Refill Box


Mission Overview

The orbiter Endeavour began its 10-day STS-57 mission on June 21, 1993. The mission was originally scheduled to begin on April 28, 1993. Four 14-day delays occurred before the actual launch on June 21. The mission terminated with the landing of Endeavour on July 1. A six- member crew flew onboard the Shuttle.

The primary mission objective was to retrieve the European Space Agency's European Carrier (EURECA) satellite. The mission had several secondary objectives, one of which was to carry a group of experiment payloads contained within the SPACEHAB facility. SPACEHAB is a commercially developed laboratory that augments the Shuttle's middeck capacity, providing experiment rack space that can be accessed and tended by crew members.

One of the payloads within SPACEHAB was the third in the series of Physiological Systems Experiment (PSE.03) payloads. PSE.03 was jointly sponsored by the NASA Center for Cell Research and a commercial partner, ConvaTec, a Bristol-Myers Squibb company.

Life Sciences Research Objectives

The PSE.03 payload was designed to study the roles of two growth factors involved in accelerating or enhancing tissue repair. Microgravity, like certain conditions on Earth, appears to slow down the process of tissue repair. Studies carried out on the Russian Cosmos 2044 biosatellite mission have suggested that muscle and bone repair are slower in microgravity. Collagen metabolism in unwounded skin is also known to be altered in microgravity. Since wound healing is dependent on adequate collagen deposition in the vicinity of the wound, it is likely that skin healing will also be altered in microgravity. The results of the experiment may help dermatologists to devise therapies for astronauts who receive skin or soft-tissue injuries during long-duration space flight. Data gathered during the STS-57 mission was also expected to be useful in developing skin treatments for burn victims, diabetics, elderly surgical patients, bed-sore sufferers, and other skin-injury patients on Earth.

Life Sciences Payload

Organisms
The experiment was conducted on adult male rats (Rattus norvegicus) belonging to the Fischer 344 strain. This strain of rat was flown for the first time on this mission in order to satisfy space, weight, and food availability restrictions. Rats of this strain were selected because they consume less food and water than Sprague-Dawley rats consume, and therefore gain less weight in a given period of time. Use of the Fischer 344 strain allowed the flight of adult rats without having to reduce the size of the sample. Twelve rats were used in the flight group, while 44 rats were used in ground control groups.

Hardware
The rats were housed in Animal Enclosure Modules (AEMs). An Ambient Temperature Recorder (ATR-4) was flown along with the AEMs to record the temperature of the rat cages. For general descriptions of the AEM and the ATR-4, see PSE.02.

Operations

Preflight
The main objective of the mission, retrieval of the EURECA satellite, meant that the Shuttle had a narrow launch window on any particular day. Each delay required the launch time to be moved ahead by 30 minutes for the next designated launch day. Correspondingly, each of the four delays required the animals' day/night cycle, which was set to correspond to Shuttle launch time, to be moved ahead by seven hours.

As in the PSE.02 experiment, upon receipt at Kennedy Space Center, the animals not assigned to a vivarium control group were placed in the Elevated Temperature Equilibrium Group, which was allowed to acclimate to 28 °C for at least seven days prior to launch. The flight group of rats was chosen from the elevated temperature group two days before launch.

Preflight experiment procedures included the implantation of growth factors into six different sites in each of the 12 rats. Two days before the launch, 20 rats, matched by weight into pairs, were selected from a group of animals maintained at 28 °C. About a day later, these 20 rats were anesthetized and sterile polyvinyl alcohol sponges, containing timed-release pellets, were surgically implanted into six areas in the subcutaneous tissue of the abdomen.

The pellets contained either growth factor A, growth factor B, or a placebo. One animal in each of the matched pairs was implanted with pellets that began releasing the growth factors or placebo immediately after implantation. The other animal in each pair was implanted with pellets coated with a substance that dissolved slowly, releasing the growth factors or placebo only after the rats had entered microgravity. Using two different kinds of pellets allowed scientists to differentiate between the growth factor-induced tissue repair and wound healing during the period from surgery to launch and during the period in microgravity. Previous investigations that used only a pellet that released growth factor immediately obfuscated the results because the healing process began before exposure to microgravity. Approximately five hours after implantation, the animals were injected with calcein.

The flight group of 12 rats was chosen from the 20 that were implanted with pellets. The remaining eight rats served as the basal control group.

Inflight
There were four groups of control rats on the ground (Table 8). The basal control group was euthanized immediately after launch in order to obtain baseline physiological data. The delayed synchronous control group was maintained in AEMs within the Orbiter Environmental Simulator (OES). The OES is a modified environmental chamber at Kennedy Space Center whose temperature, humidity, and CO2 level are electronically controlled based on downlinked environmental data from the orbiter. Thus the animals within the chamber are exposed to environmental conditions that are similar to those experienced by the flight group during the mission. The two remaining control groups were housed in vivarium cages, one at 28 °C and the other at 22 °C. The vivarium animals received the same surgical treatment as did the flight and delayed synchronous control groups.


Table 8. Flight and Conrol Groups for PSE.03 Rodents. (Click to enlarge)

The crew made daily observations of the animals, verified that the experiment hardware was functioning normally, and downlinked daily recordings of temperature data, which were used to control the Orbiter Environmental Stimulator on the ground.

On the first flight day, the crew reported a malfunction in the switch that automatically set the day and night light cycle in one of the AEMs. For the remainder of the flight, the crew manually switched the light cycle on and off.

Postflight
The animals were removed from the Shuttle about three hours after landing. They were weighed, subjected to a health check, and injected either with a saline solution or a mixture of hypothalamic releasing hormones. Approximately half an hour later, they were euthanized. The tissues surrounding the surgical implantation sites were examined to determine the effect of the growth factors on tissue repair. All the ground control groups were euthanized 48 hours after the flight groups.

Results

Both growth factors showed positive effects in the ground control rats, but only the immediate-release pellets of the first growth factor and the delayed-release pellets of the second growth factor had a significant, positive effect on the flight rats. These results may be due to the two-day delay in the Shuttle launch, which caused the growth factors to be released earlier during space flight than planned. Microgravity significantly reduced wound collagen concentration, regardless of the treatment group. Overall, the results show that a highly standardized wound repair process in young rats is significantly altered by space flight.

Additional Reading

NASA. STS-57 Press Kit, June 1993. Contained in NASA Space Shuttle Launches Web site: http://www.ksc.nasa.gov/shuttle/missions/missions.html.