scholarly journals On the biomechanical properties of osteosarcoma cells and their environment

2019 ◽  
Vol 63 (1-2) ◽  
pp. 1-8 ◽  
Author(s):  
Daniel A. Müller ◽  
Unai Silvan

Although rare among the general population, bone malignancies have a high rate of incidence among children and adolescents and are associated with high mortality rates. Osteosarcoma (also known as osteogenic sarcoma) is the most frequent primary cancer of bone and shows a high tendency to metastasize to the lung. Despite the frequent use of osteosarcoma-derived cell lines in basic biomechanical research and for the evaluation of cell responses to new biomaterials, the mechanical phenotype and the differences between osteosarcoma cells and related cell types, such as mesenchymal cells, osteoblasts and osteocytes, remain largely unknown. In the present review we summarize current knowledge of the biophysical and mechanical properties of the niche of primary osteosarcomas and of the malignant cells, and discuss the impact of these features on the progression of malignancy.

2018 ◽  
Vol 4 (1) ◽  
pp. 453-456
Author(s):  
Ralf Kemkemer ◽  
Kerstin Frey ◽  
Alena Fischer ◽  
Rumen Krastev

AbstractSurface topographies are often discussed as an important parameter influencing basic cell behavior. Whereas most in-vitro studies deal with microstructures with sharp edges, smooth, curved microscale topographies might be more relevant concerning in-vivo situations. Addressing the lack of highly defined surfaces with varying curvature, we present a topography chip system with 3D curved features of varying spacing, curvature radii as well as varying overall dimensions of curved surfaces. The CurvChip is produced by low-cost photolithography with thermal reflow, subsequent (repetitive) PDMS molding and hot embossing. The platform facilitates the systematic invitro investigation of the impact of substrate curvature on cell types like epithelial, endothelial, smooth muscle cells, or stem cells. Such investigations will not only help to further understand the mechanism of curvature sensation but may also contribute to optimize cellmaterial interactions in the field of regenerative medicine.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sarah S. Wilson ◽  
Martha Mayo ◽  
Terry Melim ◽  
Heather Knight ◽  
Lori Patnaude ◽  
...  

Background & AimsDiligent side-by-side comparisons of how different methodologies affect growth efficiency and quality of intestinal colonoids have not been performed leaving a gap in our current knowledge. Here, we summarize our efforts to optimize culture conditions for improved growth and functional differentiation of mouse and human colon organoids.MethodsMouse and human colon organoids were grown in four different media. Media-dependent long-term growth was measured by quantifying surviving organoids via imaging and a cell viability readout over five passages. The impact of diverse media on differentiation was assessed by quantifying the number of epithelial cell types using markers for enterocytes, stem cells, Goblet cells, and enteroendocrine cells by qPCR and histology upon removal of growth factors.ResultsIn contrast to Wnt3a-conditioned media, media supplemented with recombinant Wnt3a alone did not support long-term survival of human or mouse colon organoids. Mechanistically, this observation can be attributed to the fact that recombinant Wnt3a did not support stem cell survival or proliferation as demonstrated by decreased LGR5 and Ki67 expression. When monitoring expression of markers for epithelial cell types, the highest level of organoid differentiation was observed after combined removal of Wnt3a, Noggin, and R-spondin from Wnta3a-conditioned media cultures.ConclusionOur study defined Wnt3a-containing conditioned media as optimal for growth and survival of human and mouse organoids. Furthermore, we established that the combined removal of Wnt3a, Noggin, and R-spondin results in optimal differentiation. This study provides a step forward in optimizing conditions for intestinal organoid growth to improve standardization and reproducibility of this model platform.


2021 ◽  
Vol 9 (4) ◽  
pp. 58
Author(s):  
Raquel Perez-Gomez

A novel coronavirus (SARS-CoV-2) emerged towards the end of 2019 that caused a severe respiratory disease in humans called COVID-19. It led to a pandemic with a high rate of morbidity and mortality that is ongoing and threatening humankind. Most of the mutations occurring in SARS-CoV-2 are synonymous or deleterious, but a few of them produce improved viral functions. The first known mutation associated with higher transmissibility, D614G, was detected in early 2020. Since then, the virus has evolved; new mutations have occurred, and many variants have been described. Depending on the genes affected and the location of the mutations, they could provide altered infectivity, transmissibility, or immune escape. To date, mutations that cause variations in the SARS-CoV-2 spike protein have been among the most studied because of the protein’s role in the initial virus–cell contact and because it is the most variable region in the virus genome. Some concerning mutations associated with an impact on viral fitness have been described in the Spike protein, such as D614G, N501Y, E484K, K417N/T, L452R, and P681R, among others. To understand the impact of the infectivity and antigenicity of the virus, the mutation landscape of SARS-CoV-2 has been under constant global scrutiny. The virus variants are defined according to their origin, their genetic profile (some characteristic mutations prevalent in the lineage), and the severity of the disease they produce, which determines the level of concern. If they increase fitness, new variants can outcompete others in the population. The Alpha variant was more transmissible than previous versions and quickly spread globally. The Beta and Gamma variants accumulated mutations that partially escape the immune defenses and affect the effectiveness of vaccines. Nowadays, the Delta variant, identified around March 2021, has spread and displaced the other variants, becoming the most concerning of all lineages that have emerged. The Delta variant has a particular genetic profile, bearing unique mutations, such as T478K in the spike protein and M203R in the nucleocapsid. This review summarizes the current knowledge of the different mutations that have appeared in SARS-CoV-2, mainly on the spike protein. It analyzes their impact on the protein function and, subsequently, on the level of concern of different variants and their importance in the ongoing pandemic.


2019 ◽  
Vol 30 (7) ◽  
pp. 887-898 ◽  
Author(s):  
Claude N. Holenstein ◽  
Aron Horvath ◽  
Barbara Schär ◽  
Angelina D. Schoenenberger ◽  
Maja Bollhalder ◽  
...  

Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate remains below 30%. In the present work, we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells. With that aim, we used two paired osteosarcoma cell lines, with each one comprising a parental line with low metastatic potential and its experimentally selected, highly metastatic form. Mechanical characterization was performed by means of atomic force microscopy, tensile biaxial deformation, and real-time deformability, and cell traction was measured using two-dimensional and micropost-based traction force microscopy. Our results reveal that the low metastatic osteosarcoma cells display larger spreading sizes and generate higher forces than the experimentally selected, highly malignant variants. In turn, the outcome of cell stiffness measurements strongly depends on the method used and the state of the probed cell, indicating that only a set of phenotyping methods provides the full picture of cell mechanics.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Claudia Ulbrich ◽  
Markus Wehland ◽  
Jessica Pietsch ◽  
Ganna Aleshcheva ◽  
Petra Wise ◽  
...  

How microgravity affects the biology of human cells and the formation of 3D cell cultures in real and simulated microgravity (r- and s-µg) is currently a hot topic in biomedicine. In r- and s-µg, various cell types were found to form 3D structures. This review will focus on the current knowledge of tissue engineering in space and on Earth using systems such as the random positioning machine (RPM), the 2D-clinostat, or the NASA-developed rotating wall vessel bioreactor (RWV) to create tissue from bone, tumor, and mesenchymal stem cells. To understand the development of 3D structures,in vitroexperiments using s-µgdevices can provide valuable information about modulations in signal-transduction, cell adhesion, or extracellular matrix induced by altered gravity conditions. These systems also facilitate the analysis of the impact of growth factors, hormones, or drugs on these tissue-like constructs. Progress has been made in bone tissue engineering using the RWV, and multicellular tumor spheroids (MCTS), formed in both r- and s-µg, have been reported and were analyzed in depth. Currently, these MCTS are available for drug testing and proteomic investigations. This review provides an overview of the influence ofµgon the aforementioned cells and an outlook for future perspectives in tissue engineering.


2021 ◽  
Vol 15 ◽  
Author(s):  
Felipe A. Bustamante-Barrientos ◽  
Maxs Méndez-Ruette ◽  
Alexander Ortloff ◽  
Patricia Luz-Crawford ◽  
Francisco J. Rivera ◽  
...  

Estrogens and estrogen-like molecules can modify the biology of several cell types. Estrogen receptors alpha (ERα) and beta (ERβ) belong to the so-called classical family of estrogen receptors, while the G protein-coupled estrogen receptor 1 (GPER-1) represents a non-classical estrogen receptor mainly located in the plasma membrane. As estrogen receptors are ubiquitously distributed, they can modulate cell proliferation, differentiation, and survival in several tissues and organs, including the central nervous system (CNS). Estrogens can exert neuroprotective roles by acting as anti-oxidants, promoting DNA repair, inducing the expression of growth factors, and modulating cerebral blood flow. Additionally, estrogen-dependent signaling pathways are involved in regulating the balance between proliferation and differentiation of neural stem/progenitor cells (NSPCs), thus influencing neurogenic processes. Since several estrogen-based therapies are used nowadays and estrogen-like molecules, including phytoestrogens and xenoestrogens, are omnipresent in our environment, estrogen-dependent changes in cell biology and tissue homeostasis have gained attention in human health and disease. This article provides a comprehensive literature review on the current knowledge of estrogen and estrogen-like molecules and their impact on cell survival and neurodegeneration, as well as their role in NSPCs proliferation/differentiation balance and neurogenesis.


Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 255
Author(s):  
Claudia Müller ◽  
Rafał Hrynkiewicz ◽  
Dominika Bębnowska ◽  
Jaime Maldonado ◽  
Massimiliano Baratelli ◽  
...  

In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits (Oryctolagus cuniculus) emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have died after infection. The emergence of genetically-different virus variants (RHDV GI.1 and GI.2) indicated the very high variability of RHDV. Moreover, with these variants, the host range broadened to hare species (Lepus). The circulation of RHDV genotypes displays different virulences and a limited induction of cross-protective immunity. Interestingly, juvenile rabbits (<9 weeks of age) with an immature immune system display a general resistance to RHDV GI.1, and a limited resistance to RHDV GI.2 strains, whereas less than 3% of adult rabbits survive an infection by either RHDV GI.1. or GI.2. Several not-yet fully understood phenomena characterize the RHD. A very low infection dose followed by an extremely rapid viral replication could be simplified to the induction of a disseminated intravascular coagulopathy (DIC), a severe loss of lymphocytes—especially T-cells—and death within 36 to 72 h post infection. On the other hand, in animals surviving the infection or after vaccination, very high titers of RHDV-neutralizing antibodies were induced. Several studies have been conducted in order to deepen the knowledge about the virus’ genetics, epidemiology, RHDV-induced pathology, and the anti-RHDV immune responses of rabbits in order to understand the phenomenon of the juvenile resistance to this virus. Moreover, several approaches have been used to produce efficient vaccines in order to prevent an infection with RHDV. In this review, we discuss the current knowledge about anti-RHDV resistance and immunity, RHDV vaccination, and the further need to establish rationally-based RHDV vaccines.


2020 ◽  
Vol 15 (3) ◽  
pp. 187-201 ◽  
Author(s):  
Sunil K. Dubey ◽  
Amit Alexander ◽  
Munnangi Sivaram ◽  
Mukta Agrawal ◽  
Gautam Singhvi ◽  
...  

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.


2017 ◽  
Vol 45 (10) ◽  
pp. 1607-1618 ◽  
Author(s):  
Seung Yun Lee ◽  
Sunho Jung ◽  
Sangdo Oh ◽  
Seong Hoon Park

We proposed that a moderator, others' similarity, would determine the impact of high participation rates of others on an individual's charitable behavior, and aimed to show that this moderator would work through the diffusion of responsibility motive. Participants (N = 152 undergraduate students) completed measures of charitable behavior and diffusion of responsibility, after being assigned to 1 of 2 conditions where a set percentage of other students (manipulated as either similar undergraduate students or dissimilar graduate students) were stated to have already donated to a charitable campaign (high contribution condition = 70% participation, low contribution condition = 30% participation). Our results showed that the high participation rate of others increased an individual's charitable behavior when the others in question were similar to that individual, but not when the others were dissimilar. In addition, the high rate of participation by others increased the diffusion of responsibility motive when the others in question were dissimilar to that individual, leading to a negative effect on that individual's charitable behavior.


Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.


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