RCCS Bioreactor-Based Modelled Microgravity Induces Significant Changes on<i>In Vitro</i>3D Neuroglial Cell Cultures

Morabito, Caterina; Steimberg, Nathalie; Mazzoleni, Giovanna; Guarnieri, Simone; Fanò-Illic, Giorgio; Mariggiò, Maria Addolorata

doi:10.1155/2015/754283

Cited by 42 publications

(44 citation statements)

References 42 publications

(43 reference statements)

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“…Why can the 3D rotary suspension culture significantly augment both megakaryopoiesis and thrombopoiesis compared with the static culture? The rotary suspension culture has been shown to be able to generate shear stress and simulate microgravity in our and other studies [13,14,27,28]. We speculated that the shear stress generated in this system facilitates both platelet generation and release, as described previously, both in the bone marrow [15] and under other in vitro conditions [6][7][8][9].…”

Section: Discussionsupporting

confidence: 61%

Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System

Yang

Liu

Lei

et al. 2015

Stem Cells Translational Medicine

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Platelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of the platelet supply limits the care of patients. Although derivation of clinical-scale platelets in vitro could provide a new source for transfusion, the devices and procedures for deriving scalable platelets for clinical applications have not been established. In the present study, we found that a rotary cell culture system (RCCS) can potentiate megakaryopoiesis and significantly improve the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the RCCS improved platelet generation efficiency by as much as ∼3.7-fold compared with static conditions. Shear force, simulated microgravity, and better diffusion of nutrients and oxygen from the RCCS, altogether, might account for the improved efficient platelet generation. The cost-effective and highly controllable strategy and methodology represent an important step toward large-scale platelet production for future biomedical and clinical applications. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:175-185 SIGNIFICANCEPlatelet transfusion has been widely used in patients undergoing chemotherapy or radiotherapy; however, the shortage of platelet supply limits the care of patients. Thus, derivation of clinicalscale platelets in vitro would provide a new source for transfusion. The present study evaluated a rotary suspension cell culture system that was able to potentiate megakaryopoiesis and significantly improved the efficiency of platelet generation. When used with chemical compounds and growth factors identified via small-scale screening, the three-dimensional system improved platelet generation efficiency compared with the static condition. The three-dimensional device and the strategy developed in the present study should markedly improve the generation of large-scale platelets for use in future biomedical and clinical settings.

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Section: Discussionsupporting

confidence: 61%

Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System

Yang

Liu

Lei

et al. 2015

Stem Cells Translational Medicine

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“…When these cell aggregates were enzymatically dissociated and cultured in a TCP after 48 hours in microgravity, cells took 48 hours to adhere ( Fig 1G , Day 2) while cells from static cultures adhered within 24 hours ( Fig 1G , Day 1) and produced confluent cultures by day 4. Microgravity has been shown to affect several cell functions [ 7 ] and the expression or functioning of cell adhesion molecules could be affected [ 8 ] reducing the number of DLD-1 cells that could adhere to the TCP. When such cell aggregates were plated in TCP without enzymatic dissociation, the morphology of DLD-1 cells was altered ( Fig 1H and 1I ).…”

Section: Resultsmentioning

confidence: 99%

Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks

et al. 2015

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Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated) and 2542 (downregulated) genes (>2 fold) in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated) and 444 (downregulated) genes (>2 fold) under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2.

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“…A total of 12 bioreactors were used (total volume, 55 ml), each equipped with a gas-exchange membrane and incubated at 37˚C with 5% CO 2 . The bottom of the RCCS bioreactor was designed with a silicone membrane and prevented the formation of bubbles (28). Cells in the RCCS bioreactor were grown on cytodex-3 microcarrier beads (Sigma-Alrich; Merck KGaA) to provide a solid support pretreated with phosphate buffered saline (PBS) and 75% ethanol, and stored at 4˚C.…”

Section: Methodsmentioning

confidence: 99%

Effect of simulated microgravity on metabolism of HGC‑27 gastric cancer cells

et al. 2020

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The understanding into the pathogenesis and treatment of gastric cancer has improved in recent years; however, a number of limitations have delayed the development of effective treatment. Cancer cells can undergo glycolysis and inhibit oxidative phosphorylation in the presence of oxygen (Warburg effect). Previous studies have demonstrated that a rotary cell culture system (RCCS) can induce glycolytic metabolism. In addition, the potential of regulating cancer cells by targeting their metabolites has led to the rapid development of metabolomics. In the present study, human HGC-27 gastric cancer cells were cultured in a RCCS bioreactor, simulating weightlessness. Subsequently, liquid chromatography-mass spectrometry was used to examine the effects of simulated microgravity (SMG) on the metabolism of HGC-27 cells. A total of 67 differentially regulated metabolites were identified, including upregulated and downregulated metabolites. Compared with the normal gravity group, phosphatidyl ethanolamine, phosphatidyl choline, arachidonic acid and sphinganine were significantly upregulated in SMG conditions, whereas sphingomyelin, phosphatidyl serine, phosphatidic acid, L-proline, creatine, pantothenic acid, oxidized glutathione, adenosine diphosphate and adenosine triphosphate were significantly downregulated. The Human Metabolome Database compound analysis revealed that lipids and lipid-like metabolites were primarily affected in an SMG environment in the present study. Overall, the findings of the present study may aid our understanding of gastric cancer by identifying the underlying mechanisms of metabolism of the disease under SMG.

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RCCS Bioreactor-Based Modelled Microgravity Induces Significant Changes onIn Vitro3D Neuroglial Cell Cultures

Cited by 42 publications

References 42 publications

Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System

Integrated Biophysical and Biochemical Signals Augment Megakaryopoiesis and Thrombopoiesis in a Three-Dimensional Rotary Culture System

Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks

Effect of simulated microgravity on metabolism of HGC‑27 gastric cancer cells

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