Cell Sensitivity to Gravity

Cogoli, Augusto; Tschopp, Alexander; Fuchs-Bislin, P

doi:10.1126/science.6729481

Cited by 285 publications

(142 citation statements)

References 2 publications

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“…[1][2][3][4][5][6][7] For a long time, it has been clear that microgravity induces alterations in human cells. [8][9][10] However, the corresponding mechanisms are still unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Grimm

Wehland

Pietsch

et al. 2014

Tissue Engineering Part B: Reviews

121

137

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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.

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“…[1][2][3][4][5][6][7] For a long time, it has been clear that microgravity induces alterations in human cells. [8][9][10] However, the corresponding mechanisms are still unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Grimm

Wehland

Pietsch

et al. 2014

Tissue Engineering Part B: Reviews

121

137

View full text Add to dashboard Cite

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“…Especially for T lymphocytes, it is known that exposure of cells in culture to actual or modelled low gravity is often accompanied by a major inhibitory effect, remarkably reducing their mitogenic activation process (Cogoli et al 1984) and severely altering growth rate, cytokine production, gene expression, cytoskeletal structures, and motility (for reviews, see Cogoli 1993Cogoli and Cogoli-Greuter 1997;Lewis 2002;Cogoli-Greuter 2004). Furthermore, it has been demonstrated that human lymphocytes are forced to apoptosis in modelled low gravity, through a pathway based on calciumdependent 5-LOX activation, mitochondrial membrane disruption, and cytochrome c release, followed by caspase activation and cell death (Maccarrone et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Cytoskeleton changes and impaired motility of monocytes at modelled low gravity

et al. 2006

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Summary. Investigations performed in space have shown that gravity changes affect important cellular mechanisms like proliferation, differentiation, genetic expression, cytoskeletal architecture, and motility in lymphocytes, monocytes, and other mammalian cells. In particular, a dramatic depression of the mitogenic in vitro activation of human peripheral blood lymphocytes was observed at low gravity. The hypothesis of the present work is that a reduced interaction between T lymphocytes and monocytes, essential for the second signalling pathway, might be one of the reasons for the observed depression of the in vitro activation of human lymphocytes. Cell motility and with it a continuous rearrangement of the cytoskeletal network within the cell is essential for cell-tocell contacts. Whereas nonactivated lymphocytes in suspension are highly motile at low gravity, no data are available so far on the motility of adherent monocytes. It thus can be argued that impaired monocyte locomotion and cytoskeletal changes could be responsible for a reduced interaction of monocytes with T lymphocytes. In this study, the locomotion ability of J-111 cells, an adherent monocyte cell line, attached to colloidal gold particles on coverslips and exposed to modelled low gravity in the random positioning machine was found to be severely reduced compared with that of controls and the structures of actin, tubulin, and vinculin were affected.

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“…Several investigations conducted in space laboratories and with instruments averaging the gravity vector, and thus simulating conditions of reduced gravity, have shown that isolated cells may change their behavior under altered gravitational conditions. Loss of cell activation [Cogoli et al, 1984], perturbation of signal transduction [Schmitt et al, 1996;Hashemi et al, 1999] and modification of genetic expression [Walther et al, 1998;Hammond et al, 1999] have been described. This suggests that some of the mechanisms at the roots of the systemic effects observed in weightlessness, such as depression of the immune system [Gmü nder and Cogoli, 1996] …”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

et al. 2006

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Gravity acts permanently on organisms as either static or dynamic stimulation. Understanding the influence of gravitational and mechanical stimuli on biological systems is an intriguing scientific problem. More than two decades of life science studies in low g, either real or modeled by clinostats, as well as experimentation with devices simulating different types of controlled mechanical stimuli, have shown that important biological functions are altered at the single cell level. Here, we show that the human leukemic line FLG 29.1, characterized as an osteoclastic precursor model, is directly sensitive to gravitational unloading, modeled by a random positioning machine (RPM). The phenotypic expression of cytoskeletal proteins, osteoclastic markers, and factors regulating apoptosis was investigated using histochemical and immunohistochemical methods, while the expression of the corresponding genes was analyzed using RT-PCR. A quantitative bone resorption assay was performed. Autofluorescence spectroscopy and imaging were applied to gain information on cell metabolism. The results show that modeled hypogravity may trigger both differentiation and apoptosis in FLG 29.1 cells. Indeed, when comparing RPM versus 1 Â g cultures, in the former we found cytoskeletal alterations and a marked increase in apoptosis, but the surviving cells showed an osteoclastic-like morphology, overexpression of osteoclastic markers and the ability to resorb bone. In particular, the overexpression of both RANK and its ligand RANKL, maintained even after return to 1 Â g conditions, is consistent with the firing of a differentiation process via a paracrine/autocrine mechanism. J. Cell. Biochem. 98: 65-80, 2006. ß 2005 Wiley-Liss, Inc.Key words: weightlessness; preosteoclastic differentiation; apoptosis; bone resorption; osteoporosis; gene expressionThe importance of gravity in modulating some biological processes, such as plant gravitropism and the adaptation of the vertebrate skeleton in relation to its load-bearing function, has long been known. Nevertheless, the role of gravity and other mechanical factors in biological processes is far from clear. A weightless environment is a powerful tool for understanding this role and for studying the related cellular and molecular mechanisms. Several investigations conducted in space laboratories and with instruments averaging the gravity vector, and thus simulating conditions of reduced gravity, have shown that isolated cells may change their behavior under altered gravitational conditions. Loss of cell activation [Cogoli et al., 1984], perturbation of signal transduction [Schmitt et al., 1996;Hashemi et al., 1999] and modification of genetic expression [Walther et al., 1998;Hammond et al., 1999] have been described. This suggests that some of the mechanisms at the roots of the systemic effects observed in weightlessness, such as depression of the immune system [Gmü nder and Cogoli, 1996]

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Cell Sensitivity to Gravity

Cited by 285 publications

References 2 publications

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

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

Cytoskeleton changes and impaired motility of monocytes at modelled low gravity

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

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