Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

Abstract

Tissue engineering in simulated (s-) and real microgravity (r-mg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-mg in Space or to s-mg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

Key Proteins Involved in Spheroid Formation and Angiogenesis in Endothelial Cells After Long-Term Exposure to Simulated Microgravity

“…Randomizing the gravity vector by the RPM keeps human cells floating in the medium and allows to study aspects of annulling gravity. A part of the incubated cells detaches from the bottom of a culture flask and forms 3D aggregates like they are observed after spaceflights [2, 4, 5, 19]. Even though in contrast to a stay in space, sheer forces are produced on the RPM, multicellular spheroids and tubular structures are formed in both conditions [18-20].…”

Identifications of novel mechanisms in breast cancer cells involving duct-like multicellular spheroid formation after exposure to the Random Positioning Machine

“…This different growth behavior was also found in endothelial cells and thyroid cells671322. Morphology and gene expression patterns of AD and MCS cells were analyzed in comparison to each other and to cells grown in a normal laboratory incubator as 1  g (gravity)-controls.…”

Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

“…However, the inability to adequately oxygenate the cells continues to be a major limiting factor (2). This is where culture techniques, originally designed for space flight studies, may offer a distinct advantage (14,24–30). Hepatocytes grown on Earth in NASA’s rotating wall vessel suspension culture vessels form three-dimensional colonies that maintain their function for at least several weeks (14,15,24).…”

“…Hepatocytes grown on Earth in NASA’s rotating wall vessel suspension culture vessels form three-dimensional colonies that maintain their function for at least several weeks (14,15,24). These cell colonies closely resemble and function like natural cells in the human body, which makes them excellent candidates for preclinical drug testing (14,24–30).

The question to be addressed is whether space flight derived technologies have the potential to predict and prevent the morbidity, mortality and staggering cost of incidents where current methods fail to detect toxic pharmaceutical side effects premarket?

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