Results of Ground and Space Experiments

The cell culture biotechnology program encompasses a wide range of research topics, from cancer cells to parasites, from chondrocytes to lymphocytes. Originally, research focused on the generation of three-dimensional cultured tissue and on the rough characterization and comparison of these engineered tissues to natural tissues, envisaging the commercial exploitation of space for generating large amounts of tissue. Although some scientific success in this area has been achieved both in space and in ground-

based experiments, the commercialization of space products has not been successful yet.

Many ground-based studies have been performed using bioreactors for exploring cellular and tissue responses to low-stress growth environments and simulated microgravity. These systems have been used primarily to produce three-dimensional self-assembling aggregates that retain some of the cell-cell interactions present in tissues. A wide variety of culture systems have been tested, leading to several advances, such as the propagation of parasites and studies on impaired activation of lymphocytes in space (see Chapter 4). Investigators have also compiled a large list of tissues that have been cultured in bioreactors, including cancer cells, cartilage, liver, kidney, lymphoid tissue, thyroid, skin, pancreatic islet cells, neuroendocrine cells, hematopoietic cells, and intestinal epithelium, as well as microorganisms (Figure 8-02).

Figure 8-02. The Generic Bioprocessing Apparatus on board the Spacelab Science Module in the Space Shuttle Columbia (STS-94), shortly after arriving on orbit. The bioprocessing reactions involved sequential mixing of fluids for phase processing, incubation, optical monitoring, and temperature storage. This facility could host up to 132 individual experiments. Experiments included studies of how collagen fibers could be used more effectively as artificial skin or blood vessels, how the assembly of liposomes and virus capsids could be used to target a drug to specific tumors, or how mineralization occurs and influences the embiyonic bone tissue of rodents. Photo courtesy of NASA.

Figure 8-02. The Generic Bioprocessing Apparatus on board the Spacelab Science Module in the Space Shuttle Columbia (STS-94), shortly after arriving on orbit. The bioprocessing reactions involved sequential mixing of fluids for phase processing, incubation, optical monitoring, and temperature storage. This facility could host up to 132 individual experiments. Experiments included studies of how collagen fibers could be used more effectively as artificial skin or blood vessels, how the assembly of liposomes and virus capsids could be used to target a drug to specific tumors, or how mineralization occurs and influences the embiyonic bone tissue of rodents. Photo courtesy of NASA.

To date, studies on cell cultures in space in have demonstrated that microgravity and the space environment affect cell shape, signal transduction, replication and proliferation, gene expression, apoptosis, and synthesis and orientation of intracellular and extracellular macromolecules (see Chapter 4, and the following review articles: Dickson 1991, Moore and Cogoli 1996, Cogoli and Cogoli-Greuter 1997, Lewis et al. 1997, Freed et al. 1997, Hammond et al. 1999). Cell culture technology has made substantial contributions to the artificial engineering and growth of human cartilage, cardiac muscle, and kidney tissue. Macromolecular studies of insulin crystals grown in space have enabled researchers to obtain a previously unavailable molecular model that can be used to develop more effective drugs for diabetic patients (see this Chapter, Section 3.3).

2.3 Limitations

At the same time, tremendous progress has also been made in three-dimensional tissue development in normal gravity on Earth, using, for example, scaffolds and extracellular matrix gels. In experiments done in space, cell cultures experience a different gravitational environment, which reduces convection, buoyancy-driven flows, and sedimentation (see Chapter 1, Section 2.2), and it is difficult to separate the specific factor(s) causing differences between space- and Earth-grown samples. Researchers are also limited by the difficulties inherent in distinguishing the effects of launch, flight, and reentry on samples. As for the other areas of space biology, studies on cell cultures in space require experimental controls. These controls include the use of bioreactors on Earth, culture bags in microgravity, bioreactors in space, three-dimensional structures grown on Earth from scaffolds, and the same experimental setup operated in an onboard 1-g centrifuge.

Bioreactors were originally developed to simulate the microgravity environment, and provide appropriate predictions of the behavior of cells and tissue in such an environment. However, the validity of this model will not be known until comparisons are made with experiments that have been subjected to microgravity and not modified by launch and reentry. Such research is now made possible by the long-duration microgravity capability of the ISS.

Also, while bioreactors have been an important tool for generating aggregates in cell culture for three-dimensional engineered tissue, they are limited in many respects. First, the tissue synthesized is lacking many of the minor cells and elements formed within the intact organism. Second, in cell cultures, the cells that die are not generally removed, creating some artifacts. Third, tissues grown in bioreactors are not subject to the environmental signals that they might sense in situ (e.g., growth factors, vascular changes, neuromuscular changes), yet these signals are apt to change in microgravity.

In addition to these systemic and environmental drawbacks, the bioreactor has technical limitations. The limited oxygen transfer capabilities make bioreaetors inappropriate for systems with high oxygen demand. Also, it has not yet been determined if rotating-wall vessel bioreaetors can provide an appropriate environment for tissues such as osteoblasts that only grow properly when the distances between the cells are maintained.

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