Tested human liver cell functionality in microgravity, then compared the results to the typical function of duplicate cells on Earth. The findings of this experiment provided unprecedented information about the effects of microgravity on the proper function of human liver cells, offering new insight into maintaining the health of humans living and working in space. Research in this area could lead to earlier and more reliable drug candidate screening for patients in need of liver transplants.Principal Investigator(s)
National Aeronautics and Space Administration (NASA)Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)Research Benefits
Information PendingISS Expedition Duration
June 2002 - December 2002Expeditions Assigned
5Previous ISS Missions
The liver filters potentially harmful substances from the blood and breaks these substances down into water-soluble forms that can be washed from the body. It is therefore a difficult organ to treat because medications can be broken down and removed before they have an opportunity to provide effective treatment. The purpose of this experiment was to allow the investigator to observe how human liver cells react to the presence of drugs in microgravity, and to compare these results to a control experiment conducted on the ground.
To do this, human liver cells were launched inside a caddy held at freezing temperatures within a Dewar. The experiments were conducted in the CBOSS, including the BSTC, the gas supply module, and syringes. Individual cell cultures were grown in the temperature-controlled environment of the BSTC. When the experiments were complete, they were stored in the ARCTIC freezer until the end of the Expedition.
This experiment will give insight on how liver cells function in microgravity. The results will help in developing measures to further protect the health of crewmembers on extended exploration missions.Earth Applications
Human liver cells grown on Earth using traditional techniques typically form flat colonies that only function for one or two days at best. However, liver cells grown on Earth in NASA's Rotating Bioreactor form three-dimensional colonies that maintain their function for at least several weeks. These cell colonies closely resemble and function like natural cells in the human body, which makes them excellent candidates for research concerning drug metabolism and general cell function. Scientists believe that cells grown in a microgravity environment will also develop in a three-dimensional form that resembles cells in the human body. This will enable researchers to isolate and study the multiple factors that influence cellular function in microgravity and then compare the results to ground-based data obtained from the Rotating Bioreactor.
The Rotating Bioreactor is being used in the investigator's laboratory to perform drug metabolism studies. These studies are useful for determining how the human body will process a drug. In addition, quantities of drug metabolites are produced and these are required in various pharmacokinetic and toxicology studies during the course of drug development. The ultimate goal is to speed up the process that is used to make new drugs available for patients in need.
The data obtained from this investigation could also aid in the development of a liver-assist device, a machine very similar to a kidney dialysis machine. Such a device would be used to sustain the life of a patient with advanced liver disease waiting for an organ transplant.
StelSys operations will rely on hardware already on Station, including CBOSS components (EXPRESS Rack 1) and the ARCTIC freezer (EXPRESS Rack 4).
CBOSS consists of four hardware components that will provide a controlled environment for cultivating cells in vivo (outside a living body). It is intended to be an interim platform for cellular research until the permanent Biotechnology Facility is delivered to the Station.
The Biotechnology Specimen Temperature Controller (BSTC) will be used as the growing facility. Originally designed with four chambers, BSTC-303 has been reconfigured to contain one large chamber that can house 32 stationary tissue culture modules (TCMs) at temperatures between 4 and 50 degrees C (39.2-122 degrees F). The TCMs are clear Teflon bags that hold approximately 30 ml of growth media. BSTC has also has been reconfigured to include a gas purge system, carbon dioxide monitoring (provided by the front display), and an Ethernet connection to the Station computer via the EXPRESS Rack. BSTC is equipped with systems and temperature monitors that are able to detect conditions inside its chambers that could lead to fire. If a fire precursor is detected, BSTC sends a warning message to the Rack Interface Computer (RIC), as part of the RIC's health and status reporting, and the BSTC software initiates an orderly hardware shutdown.
The Gas Supply Module (GSM) provides the BSTC with gases necessary for optimal cell growth. GSM can hold up to 600 liters (634 quarts), when charged to 2,575 psi, of gas in four gas cylinders. Two supply lines offer multiple experiment support.
The Biotechnology Refrigerator (BTR), which measures 27.9 cm by 17.7 cm (10.98 in by 6.96 in) and provides storage at 4 degrees C (39.2 degrees F), preserves temperature-sensitive cell samples during launch and return on the Shuttle.
Biotechnology Cell Science Stowage 1 and 4 (BCSS-1 and -4) are designed to package and protect the experiment equipment and materials during transport on the Shuttle and during operation on Station.
The crew will transfer the cryogenically frozen samples StelSys samples to BSTC and activate the experiments, using syringes to inject cells into the samples.
BSTC and GSM were housed side by side in lockers 1 and 5, respectively, of EXPRESS Rack 4. At the end of Increment 3, BTR was transferred to EXPRESS Rack 4, as well. BSTC operates on 56 watts of power, provided during experiment operations by the rack. GSM does not use power or gas supplied by the EXPRESS Rack, but does interface with the Station computer via the EXPRESS Rack's Ethernet connection. BCSS-1 and -4, housed directly below BSTC and GSM in lockers 2 and 6, do not require support. BTR is located in EXPRESS Rack 1, locker 6. It operates on 160 watts of continuous power and Ethernet connection provided by the rack.
The samples returned from space were analyzed by specialized mass spectrometry equipment to determine the amount of drug metabolites formed by the liver cells from the drug substances added. Overall this analysis showed that the rate of metabolism by the liver cells in space was lower than that of the liver cells maintained under similar conditions on Earth. This was true for all of the drug substances tested as well as for cells from three different liver donors. These results indicate that microgravity may well retard the rate of drug metabolism in the human liver, although the mechanism for this effect is yet unknown.
Returned samples were also analyzed by gene array to determine whether genetic expression differed for cells in microgravity. Differences were found, including 9,200 of 13,000 genes that had at least two-fold greater expression in space as compared to Earth and 9,800 genes that had decreased expression in space. This large body of data is being analyzed for clues as to how liver cell function changes in specific ways in the microgravity environment of space. (Evans et al. 2009)
Nussler AK, Wang A, Neuhaus P, Fischer J, Yuan J, Liu L, Zeilinger K, Gerlach JC, Arnold PJ, Albrecht W. The suitability of hepatocyte culture models to study various aspects of drug metabolism. ALTEX-Alternatives to Animal Experimentation. 2001; 18(2): 91-101.