Cellular Biotechnology Operations Support Systems: Use of NASA Bioreactor to Study Cell Cycle Regulation: Mechanisms of Colon Carcinoma Metastasis in Microgravity (CBOSS-01-Colon) - 07.14.16
Cells grown in microgravity grow and replicate into complex structures, unlike cells grown on Earth. To better understand the mechanisms that cause the differentiation of cells in microgravity, six cell lines of common human illnesses were grown on ISS. The cells were returned to Earth and were used in the studies of several human diseases. This study is important for understanding the mechanisms needed to fight colon cancer in humans. Science Results for Everyone
Scientists often learn as much from mistakes as from successes. This investigation examined the life cycle of colon cells to better understand colon cancer. The colon carcinoma cells died on orbit, but ground-based research revealed a novel mechanism by which microgravity may kill cells. Analysis also showed that carcinoembryonic antigen (CEA) interacts with receptors on a cell membrane to reduce cell death. CEA is a protein normally found in the tissue of a developing fetus, and its presence in the blood of adults is often an indication of cancer. Its role in preventing cell death represents a significant finding for many types of cancer. Experiment Details
John Milburn Jessup, M.D., National Cancer Institute, Bethesda, DC, United States
Wyle, Integrated Science and Engineering, Houston, TX, United States
Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)
Human Exploration and Operations Mission Directorate (HEOMD)
ISS Expedition Duration
August 2001 - December 2001
A previous version of the BSTC flew on STS-86/Mir and STS-90. BTR flew on STS-89 and STS-91. Cell-growth experiments have flown on the Shuttle since STS-70.
- The CBOSS-01-Colon experiment is one of seven experiments in the CBOSS suite of experiments. The purpose of the CBOSS experiments is to support biotechnological research aboard ISS by providing a stable environment for growing cells.
- This self-contained apparatus is designed to allow multiple experiments studying various types of cells to operate simultaneously. It is a multi-component cell incubator intended to grow three-dimensional clusters of cells in microgravity.
- CBOSS-01-Colon will examine the life cycle of colon cells in order to better understand human colon cancer cells.
The purpose of the Cellular Biotechnology Operations Support System (CBOSS) study was to support biotechnological research on board ISS by providing a stable environment in which to grow cells. The system was a multi-component cell incubator intended to grow three-dimensional clusters of cells in microgravity. A self-contained apparatus, CBOSS was designed to allow multiple experiments to be performed, thereby enabling scientists to study various types of cells operating simultaneously.
In the human body, cells normally grow within a scaffolding of protein and carbohydrate fibers that creates a three dimensional structure. But outside the body, cells tend to grow in flat sheets and are incapable of duplicating the structure they normally hold, which can make them behave differently in the laboratory than they would in the body. Past research has shown that cells grown in a microgravity environment arrange themselves into three-dimensional shapes that more closely duplicate how they would behave in the body. Cell culture in microgravity thus becomes a tool for studying cells in a state that is closer to that which occurs normally in the body.
Human colorectal carcinoma cells were grown to test the hypothesis that three-dimensional growth in microgravity facilitates the reprogramming of signal transduction pathways and gene expression as cells differentiate into the two major colonic cell lineages. This differentiation is important because it may inhibit cancer growth and, if applied to developing cancers, may block the emergence of new cancer formation. The unique environment of microgravity can provide insight into growth, maturation, and death of this type of cancer cells.
Development of techniques to reliably cultivate organisms under controlled conditions is essential to understanding the effect of microgravity and radiation on living organisms and creating environmental conditioning sources for long term space flight.
In the human body cells normally grow within a scaffolding of protein and carbohydrate fibers that help create a three dimensional structure. This is how organs maintain their shape. Studying cells on Earth is difficult because outside the body cells tend to grow in flat sheets and are not capable of duplicating the structure they normally hold, which often makes them behave differently in the lab than they would in the body. Past research, however, has shown that cells grown in microgravity arrange themselves into three-dimensional shapes, more closely duplicating how they behave in the body. CBOSS-01-Colon, then, becomes very useful as a tool for studying cells in a state as close to that which occurs normally in the body.
Operational Requirements and Protocols
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. 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 EXPRESS Rack 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.
After the CBOSS hardware was installed on ISS, the crew activated the experiments and monitored the status of the experiments and hardware. Crew members used a syringe to inject cells into fresh tissue culture modules (TCMs), by using the injection ports. They also added fresh media to growing cell lines and fixatives at the end of the experiment to halt growth. When the cultures were fixed, the TCMs were transferred to the Biotechnology Refrigerator (BTR) for storage. The crew performed periodic preventive maintenance on the CBOSS components. Video and data was downloaded to the CBOSS flight control team at the Johnson Space Center's Telescience Center. CBOSS-01-Colon experiment TCMs were returned the principle investigator for in-depth analysis.
Decadal Survey Recommendations
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The CBOSS hardware supported six cell culture investigations with different detailed scientific objectives. There were problems in the growth and preservation of all of the cell lines grown on Expeditions 3 and 4. The PC12 and erythroleukemia cells did not survive well in long term culture, so no scientific results are expected from these experiments. It was found that there was more bubble formation than expected that may lead to cell death at the air-liquid interface. Although not well documented in this experiment, it was noted that poor mixing of cells/tissues and medium occurred in the other CBOSS payloads as well. Both the poor mixing and greater than expected bubble formation were important lessons learned that led to the addition of the CBOSS-Fluid Dynamics Investigation (CBOSS-FDI) to study mixing and bubble formation in microgravity on later Expeditions.
Analyses of the returned colon carcinoma cells revealed that the cells had died on orbit. However, ground-based research led to an appreciation of a novel mechanism by which microgravity may kill cells as well as of the role of tumor marker carcinoembryonic antigen (CEA) on preventing cell death. It has been shown that CEA interacts with death receptors on the cell membrane to reduce cell death. Since CEA is important to many of the cancers that afflict men and women in the United States, this is a critical finding that was in large part initiated by studies of growth in simulated microgravity. These results are not yet published, but were presented by Jessup at the Keystone Symposium on "Stem Cells, Senescence and Apoptosis" (Singapore, Oct 25 - 30, 2005). (Evans et al. 2009)
Ground Based Results Publications
Jessup JM, Frantz M, Sonmez-Alpan E, Locker J, Skena K, Waller H, Battle P, Nachman A, Bhatti, Weber ME, Thomas DA, Curbeam Jr. RL, Baker TL, Goodwin TJ. Microgravity culture reduces apoptosis and increases the differentiation of a human colorectal carcinoma cell line. In Vitro Cellular and Developmental Biology - Animal. 2000; 36(6): 367-373.
Jessup JM, Samara RN, Battle P, Laguinge LM. Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway. Clinical and Experimental Metastasis. 2004; 21: 709-17.
Laguinge LM, Lin S, Samara RN, Salesiotis AN, Jessup JM. Nitrosative Stress in Rotated Three-Dimensional Colorectal Carcinoma Cell Cultures Induces Microtubule Depolymerization and Apoptosis. Cancer Research. 2004; 64(8): 2643-8.
Jessup JM, Laguinge LM, Lin S, Samara RN, Aufman K, Battle P, Frantz M, Edmiston KH, Thomas P. Carcinoembryonic antigen induction of IL-10 and IL-6 inhibits hepatic ischemic/reperfusion injury to colorectal carcinoma cells. International Journal of Cancer. 2004; 111: 332-337.
Jessup JM, Pellis NR. NASA biotechnology: cell science in microgravity.. In Vitro Cellular and Developmental Biology - Animal. 2001; 37(2): 2. PMID: 11332737.
NASA Fact Sheet
Microscopy image of malignant colon carcinoma cell. Courtesy image of Marshall Space Flight Center.
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NASA Image: ISS003E5283 - Image of a Quad Tissue Culture Module Assembly (QTCMA) 5 on ISS Expedition 3 after activation of the cells. A syringe was used to inject cells into the pink nutrient growth media. The BSTC can hold eight of these QTCMAs, which will be used to grow human cells on ISS. When the samples completed their growth cycle, the crew transfered the QTCMAs from the BSTC to the BTR, where they were stored until they are examined at a ground-based laboratory.
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