Review
Cell & Tissue Engineering
Hyeonyu Kim, Roger D. Kamm, Gordana Vunjak-Novakovic, Joseph C. Wu
Summary: Advances in self-organizing cardiac organoids have provided a powerful tool for studying human cardiac development, cardiovascular diseases, drug testing, and transplantation. This review highlights the recent progress on multicellular cardiac organoids and introduces key readouts and tools for assessing their clinical applications.
Article
Cell Biology
Jose Luis Cortes-Sanchez, Daniela Melnik, Viviann Sandt, Stefan Kahlert, Shannon Marchal, Ian R. D. Johnson, Marco Calvaruso, Christian Liemersdorf, Simon L. Wuest, Daniela Grimm, Marcus Krueger
Summary: In the preparation of space and microgravity experiments, the use of ground-based facilities for initial experiments and feasibility studies is common. One approach to simulate microgravity conditions on Earth is to use a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices have been shown to produce results similar to those obtained in actual space experiments under real microgravity conditions. The RPM serves as a simulator of microgravity by randomizing the impact of Earth's gravity vector especially for suspended cells, and it also simulates physiological shear forces on the adherent cell layer.
Article
Engineering, Biomedical
Chul-Yong Park, Gyunggyu Lee, Gyeongmin Kim, Dong-Hun Woo, Choongseong Han, Han-Jin Park, Dong-Wook Kim, Jong-Hoon Kim, Jeong Sang Son, Ji Young Park, Hyo Jin Kim, Kyun Yoo Chi, Sang Kyum Kim
Summary: This study successfully used genome engineering and induced pluripotent stem cell (iPSC) technologies to create endothelial cells that can increase the level of coagulation factor VIII, showing promising results in treating hemophilia A in animal models. This research opens up new possibilities for gene therapy in hemophilia.
Article
Nanoscience & Nanotechnology
Xiao Han, Shijia Tang, Lin Wang, Xueqin Xu, Ruhan Yan, Sen Yan, Zhaobin Guo, Ke Hu, Tingting Yu, Mengping Li, Yuqin Li, Feimin Zhang, Ning Gu
Summary: DPSCs cultured in three-dimensional spheroids exhibited enhanced odontogenic differentiation ability, with a significant upregulation of E-cadherin and N-cadherin and enriched CD146 positive subpopulation. Furthermore, DPSCs spheroids showed a stronger osteogenic differentiation tendency than conventionally cultured two-dimensional DPSCs under the stimulation of magnetic iron oxide nanoparticles (IONPs). This suggests that a composite viscoelastic material-based 3D spheroid culture combined with mechanical/magnetic stimulation may provide new insights for dentin or bone regeneration technology.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Cian-Ru Yang, Chu-Ting Liang, Shih-Chieh Tsai, Yu-Chun Wu, Ching-Wen Liu, Hui-Hua Yang, Ting-Yuan Tu, Yueh-Chun Lee, Kuei-Yang Hsiao, Wei-Chun Chang, Wen-Lung Ma
Summary: The ACD 3D culture system is an efficient tool for supporting and evaluating the formation of tumor spheroids and tumoroids, providing good control and consistency, and mimicking the characteristics of the tumor microenvironment, especially suitable for cancer stem cell research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mathangi Madhavan, Devina Jaiswal, Sarah Karlberg, Alexis Duggan, Hassan A. A. Almarshad, Kevin P. P. Claffey, Kazunori Hoshino
Summary: Multicellular cancer spheroids are an in vitro tissue model that simulates the three-dimensional microenvironment. Older spheroids are found to have a denser internal structure, resulting in increased stiffness. This study is of great significance in understanding tumor development and treatment response.
Review
Biochemistry & Molecular Biology
Mariangela Scalise, Fabiola Marino, Luca Salerno, Eleonora Cianflone, Claudia Molinaro, Nadia Salerno, Antonella De Angelis, Giuseppe Viglietto, Konrad Urbanek, Daniele Torella
Summary: Organoids are tiny, self-organized, three-dimensional tissue cultures derived from stem cell differentiation, mimicking specific tissue structures in vitro with great potential for a variety of applications. By exploiting the ability of cells to re-aggregate and reconstruct original organ architecture, organoids have the ability to overcome limitations of traditional 2D cell cultures, showing high promise in cardiovascular research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Yijia Wang, Amanda B. Hummon
Summary: MSI is a powerful imaging tool for drug discovery, capable of analyzing a wide range of molecules in diverse samples. Its potential has been demonstrated in 3D cell culture systems, providing insights into drug compound metabolism and distribution of metabolites. The application of MSI in patient-derived organoids for personalized medicine options is also discussed in this review.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Petra M. Wise, Paolo Neviani, Stefan Riwaldt, Thomas J. Corydon, Markus Wehland, Markus Braun, Marcus Krueger, Manfred Infanger, Daniela Grimm
Summary: Researching the impact of weightlessness on the human body is crucial for space exploration. Utilizing new technologies to analyze cell-cell communication changes can provide insights into proteomic changes. Analyzing differentially expressed miRNAs in cells may reveal implications for thyroid disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Daniela Grimm, Herbert Schulz, Marcus Kruger, Jose Luis Cortes-Sanchez, Marcel Egli, Armin Kraus, Jayashree Sahana, Thomas J. Corydon, Ruth Hemmersbach, Petra M. Wise, Manfred Infanger, Markus Wehland
Summary: Cancer is a burdensome disease with high morbidity and mortality, and research in space under microgravity conditions has the potential to fight cancer and develop new therapies. Studies have shown that microgravity affects various aspects of cancer cells and can be used to create in vitro tumor models for drug development and studying cancer progression and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jeonghyun Kim, Takashi Inagaki, Junko Sunaga, Taiji Adachi, Takeo Matsumoto
Summary: This study elucidated the multicellular behaviors of osteocytic spheroids in response to osteogenesis supplements. The results showed that the supplements altered the spheroids' behaviors by affecting their size, fusion speed, and collagen embedding. Actin filaments were identified as the driving force behind these changes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biotechnology & Applied Microbiology
Laura Locatelli, Sara Castiglioni, Jeanette A. M. Maier
Summary: This review article discusses the effects of space environment on the human vasculature and the adaptive responses activated in such conditions. The study suggests that oxidative stress and mitochondrial dysfunction might be mediators of vascular alterations in space. Understanding the cellular and molecular mechanisms involved in these adaptive processes could provide insights for designing proper countermeasures for space exploration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Engineering, Biomedical
Woochan Kim, Yonghyun Gwon, Sunho Park, Hyoseong Kim, Jangho Kim
Summary: Three-dimensional stem cell culture systems have the potential to mimic complex interactions between cells and the extracellular matrix, and have unique properties that can be applied in therapeutics.
BIOACTIVE MATERIALS
(2023)
Article
Engineering, Aerospace
Ariel M. Hughes, Joshua P. Vandenbrink, John Z. Kiss
Summary: The use of plants in bioregenerative life support systems will be crucial for the future of space exploration. However, the microgravity of space can cause stress in plants and hinder their growth. This study compares the effects of microgravity on Arabidopsis thaliana seedlings grown on the International Space Station and on a rotating RPM on Earth. The results show that the RPM treatment causes less stress in the seedlings than true microgravity, and different gravitational environments affect the roles of phytochromes A and B in phototropic responses to unilateral light.
MICROGRAVITY SCIENCE AND TECHNOLOGY
(2023)
Article
Biology
Igor V. Vakhrushev, Elizaveta K. Nezhurina, Pavel A. Karalkin, Anastasia V. Tsvetkova, Nataliya S. Sergeeva, Alexander G. Majouga, Konstantin N. Yarygin
Summary: Sprouting angiogenesis is the main process of new blood vessel formation in adult mammals. Understanding its cellular and molecular mechanisms is crucial for research and medicine. A 3D in vitro approach using tissue aggregates provides an effective way to study this process and has potential applications in drug testing and tissue engineering.
Article
Psychology, Biological
Tillmann H. C. Krueger, Brigitte Leeners, Enrico Tronci, Toni Mancini, Fabian Ille, Marcel Egli, Harald Engler, Susanna Roeblitz, Helge Frieling, Christopher Sinke, Kirsten Jahn
Summary: This multisite longitudinal study investigates behavioral parameters and hormone levels in menstruating women. The study found that LH and testosterone levels increase during the pre-ovulatory phase, and methylation of the androgen receptor decreases during the mid-luteal phase. The study also found a correlation between physical condition and sexual interest with androgen receptor gene methylation level.
PHYSIOLOGY & BEHAVIOR
(2023)
Review
Cell Biology
Silja Hansen, Michelle E. McClements, Thomas J. Corydon, Robert E. MacLaren
Summary: Inherited retinal diseases (IRD) are a group of clinically and genetically diverse diseases that cause blindness in the working-age population. Gene augmentation therapies have limitations in treating IRDs, but DNA editing, particularly prime editing, shows potential in correcting different types of mutations. This review provides an overview of recent advancements in prime editing technology and discusses its potential as a treatment option for IRDs.
Article
Anatomy & Morphology
Claudia R. Cecchi, Sidsel Alsing, Gustavo P. P. Jesus, Enio A. Zacarias, Lisbeth Kjaer, Michelle S. Clement, Makiko Kumagai-Braesch, Thomas J. Corydon, Paolo Bartolini, Cibele N. Peroni, Lars Aagaard
Summary: Growth hormone (GH) deficiency is currently treated with recombinant human GH (hGH), but encapsulated cell therapy (ECT) may provide a more convenient long-term treatment strategy. This study used PiggyBac-based (PB) transposon delivery to engineer retinal pigment epithelial cells (ARPE-19) with various promoters and codon-optimization methods, and tested the secretion of GH. The results showed that ARPE-19 cells could be encapsulated in TheraCyte devices and secrete GH for at least 60 days in vitro, demonstrating the potential for further in vivo studies.
Review
Cell Biology
Thomas J. Corydon, Herbert Schulz, Peter Richter, Sebastian M. Strauch, Maik Boehmer, Dario A. Ricciardi, Markus Wehland, Marcus Krueger, Gilmar S. Erzinger, Michael Lebert, Manfred Infanger, Petra M. Wise, Daniela Grimm
Summary: Microgravity has a significant impact on the health of space explorers, affecting cell proliferation, differentiation, and growth. With the planning of deep space exploration and the commercialization of space travel, researchers are focusing on gene regulation in cells and organisms exposed to real and simulated microgravity. Cancer and metastasis research in particular benefit from these findings.
Review
Biochemistry & Molecular Biology
Urjosee Sahana, Markus Wehland, Ulf Simonsen, Herbert Schulz, Daniela Grimm
Summary: Despite recent advances in HF therapy, CV mortality, morbidity, and HFH remain challenges. Vericiguat activates sGC to improve CV function and has shown efficacy in reducing CV death and HFH in HFrEF patients. However, it has no therapeutic effect on HFpEF. Common adverse events of vericiguat include hypotension, syncope, and anemia. Larger studies are needed to investigate the potential effect in HFpEF patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Biochemistry & Molecular Biology
Daniela Grimm
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jakob Haldrup, Sofie Andersen, Alexander Rafael LaVilla Labial, Jonas Holst Wolff, Frederik Plum Frandsen, Thomas Wisbech Skov, Anne Bruun Rovsing, Ian Nielsen, Thomas Stax Jakobsen, Anne Louise Askou, Martin K. Thomsen, Thomas J. Corydon, Emil Aagaard Thomsen, Jacob Giehm Mikkelsen
Summary: Effective delivery of gene editing tools in therapeutic in vivo gene editing using CRISPR/Cas can be achieved by engineering lentivirus-derived nanoparticles (LVNPs) as carriers for Cas protein and single guide RNA (sgRNA). LVNPs facilitate precise and efficient gene editing with reduced off-target cleavage activity, making them promising vehicles for in vivo gene disruption. The proof-of-concept study in mice demonstrates the potential of LVNPs for donor-free base and prime editing without double-stranded DNA breaks.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Medicine, Research & Experimental
Ida Juhl Corydon, Bjorn Kristensen Fabian-Jessing, Thomas Stax Jakobsen, Asbjorn Cortnum Jorgensen, Emilie Grarup Jensen, Anne Louise Askou, Lars Aagaard, Thomas Juhl Corydon
Summary: The year 2023 is the 25th anniversary of the discovery of RNAi. RNAi-based therapeutics have gained significant momentum in the past decade, with five approved therapeutics targeting the liver and ongoing trials indicating the availability of more RNAi-based medicines for extra-hepatic tissues in the future. This systematic review identified a total of 90 trials published in 81 articles and 48 ongoing trials, investigating the maturation of RNAi-based therapeutics and developments in delivery platforms, administration routes, and potential targets.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Ophthalmology
Thomas Stax Jakobsen, Jakob Appel ostergaard, Mads Kjolby, Elisa Lund Birch, Toke Bek, Anders Nykjaer, Thomas J. Corydon, Anne Louise Askou
Summary: The level and localization of the multifunctional receptor sortilin in the diabetic retina were investigated, and the effect of sortilin inhibition on retinal neurodegeneration in experimental diabetes was studied. Increased levels of sortilin were observed in human and murine diabetic retinas, and sortilin was highly localized to retinal Muller cells. Sortilin inhibition effectively protected against neuronal loss in diabetic mice by reducing inner retinal thickness and the count of retinal ganglion cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Meeting Abstract
Dermatology
T. Leibing, C. Manta, J. Krzistetzko, M. Adrian, C. Kirkamm, C. Sticht, S. Tonack, H. Nolte, M. Krueger, S. Offermanns, K. Schledzewski, S. Goerdt, C. Geraud
EXPERIMENTAL DERMATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Niklas S. Jensen, Markus Wehland, Petra M. Wise, Daniela Grimm
Summary: Hypertension is a major global health burden, with an increasing prevalence due to aging populations and sedentary lifestyles. While there is evidence of the role of vitamin D in regulating blood pressure, its direct antihypertensive effect remains unclear. However, supplementing vitamin D in combination with other antihypertensive agents may have promising results.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jayashree Sahana, Jose Luis Cortes-Sanchez, Viviann Sandt, Daniela Melnik, Thomas J. Corydon, Herbert Schulz, Zexi Cai, Katja Evert, Daniela Grimm, Markus Wehland
Summary: This study cultured breast cancer cell lines MCF-7 and MDA-MB-231 under simulated microgravity conditions and investigated the gene expression pattern and cellular signaling pathways involved. The results showed that the engineered three-dimensional multicellular spheroid model can be used to study breast cancer cell behavior and evaluate the efficacy of drugs against breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Jose Luis Cortes-Sanchez, Daniela Melnik, Viviann Sandt, Stefan Kahlert, Shannon Marchal, Ian R. D. Johnson, Marco Calvaruso, Christian Liemersdorf, Simon L. Wuest, Daniela Grimm, Marcus Krueger
Summary: In the preparation of space and microgravity experiments, the use of ground-based facilities for initial experiments and feasibility studies is common. One approach to simulate microgravity conditions on Earth is to use a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices have been shown to produce results similar to those obtained in actual space experiments under real microgravity conditions. The RPM serves as a simulator of microgravity by randomizing the impact of Earth's gravity vector especially for suspended cells, and it also simulates physiological shear forces on the adherent cell layer.
