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Organoids as complex (bio)systems Fernandes, Tiago G.
Frontiers in cell and developmental biology,
08/2023, Volume:
11
Journal Article
Peer reviewed
Open access
Organoids are three-dimensional structures derived from stem cells that mimic the organization and function of specific organs, making them valuable tools for studying complex systems in biology. ...This paper explores the application of complex systems theory to understand and characterize organoids as exemplars of intricate biological systems. By identifying and analyzing common design principles observed across diverse natural, technological, and social complex systems, we can gain insights into the underlying mechanisms governing organoid behavior and function. This review outlines general design principles found in complex systems and demonstrates how these principles manifest within organoids. By acknowledging organoids as representations of complex systems, we can illuminate our understanding of their normal physiological behavior and gain valuable insights into the alterations that can lead to disease. Therefore, incorporating complex systems theory into the study of organoids may foster novel perspectives in biology and pave the way for new avenues of research and therapeutic interventions to improve human health and wellbeing.
Dental pulp represents a promising and easily accessible source of mesenchymal stem cells for clinical applications. Many studies have investigated the use of human dental pulp stem cells and stem ...cells isolated from the dental pulp of human exfoliated deciduous teeth for bone tissue engineering in vivo. However, the type of scaffold used to support the proliferation and differentiation of dental stem cells, the animal model, the type of bone defect created, and the methods for evaluation of results were extremely heterogeneous among these studies conducted. With this issue in mind, the main objective of this study is to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of human dental pulp stem cells and stem cells from human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The article search was conducted in PubMed/MEDLINE and Web of Science databases. Original research articles assessing potential of human dental pulp stem cells and SHED for in vivo bone tissue engineering, published from 1984 to November 2017, were selected and evaluated in this review according to the following eligibility criteria: published in English, assessing dental stem cells of human origin and evaluating in vivo bone tissue formation in animal models or in humans. From the initial 1576 potentially relevant articles identified, 128 were excluded due to the fact that they were duplicates and 1392 were considered ineligible as they did not meet the inclusion criteria. As a result, 56 articles remained and were fully analyzed in this systematic review. The results obtained in this systematic review open new avenues to perform bone tissue engineering for patients with bone defects and emphasize the importance of using human dental pulp stem cells and SHED to repair actual bone defects in an appropriate animal model.
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The term "cellular microenvironment" is a generic expression used to describe the complex collection of stimuli that contribute to cell and tissue functions ....
Myrmecochory-seed dispersal by ants-is a mutualistic interaction in which ants attracted by seed appendices take them away from the parental plant location, where seeds usually have better ...development odds. Not all ant species benefit plants, and the mechanisms of those divergent outcomes are still unclear, especially from the perspective of microbial third parties. Here, we explore the effects of seed manipulation on fungi communities promoted by two ant species with contrasting effects on seed germination and antimicrobial cleaning strategies. We hypothesize that: i) fungi richness is higher in seeds manipulated by Acromyrmex subterraneus (species that negatively affect seed germination), followed by unmanipulated seeds and seeds manipulated by Atta sexdens (ant species that increase seed germination) and ii) seeds manipulated by A. sexdens, Ac. subterraneus and unmanipulated seeds present dissimilar fungi compositions. We identified fungal morphotypes in three groups of seeds: i) manipulated by A. sexdens; ii) manipulated by Ac. subterraneus; iii) unmanipulated. Seeds manipulated by Ac. subterraneus exhibited higher fungal richness than those manipulated by A. sexdens and unmanipulated seeds, indicating that the ant species known to impair germination increases the fungal load on seeds. Additionally, we found that A. sexdens ants were unable to reduce fungal richness compared to unmanipulated seeds. Furthermore, fungal composition differed among all three treatments. Our results underscore the significance of ant species identity in shaping the fungal communities associated with myrmecochorous seeds. Given the potential influence of microbial infection on seed fate, we suggest considering manipulation strategies when evaluating the overall quality of an ant as a seed disperser.
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Human induced pluripotent stem (hiPS) cell culture using Essential 8™ xeno-free medium and the defined xeno-free matrix vitronectin was successfully implemented under adherent conditions. This matrix ...was able to support hiPS cell expansion either in coated plates or on polystyrene-coated microcarriers, while maintaining hiPS cell functionality and pluripotency. Importantly, scale-up of the microcarrier-based system was accomplished using a 50 mL spinner flask, under dynamic conditions. A three-level factorial design experiment was performed to identify optimal conditions in terms of a) initial cell density b) agitation speed, and c) to maximize cell yield in spinner flask cultures. A maximum cell yield of 3.5 is achieved by inoculating 55,000 cells/cm2 of microcarrier surface area and using 44 rpm, which generates a cell density of 1.4x106 cells/mL after 10 days of culture. After dynamic culture, hiPS cells maintained their typical morphology upon re-plating, exhibited pluripotency-associated marker expression as well as tri-lineage differentiation capability, which was verified by inducing their spontaneous differentiation through embryoid body formation, and subsequent downstream differentiation to specific lineages such as neural and cardiac fates was successfully accomplished. In conclusion, a scalable, robust and cost-effective xeno-free culture system was successfully developed and implemented for the scale-up production of hiPS cells.
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Human induced pluripotent stem cells (hiPSCs) represent an almost limitless source of cells for disease modelling and drug screening applications. Here we established an efficient and robust 3D ...platform for cardiomyocyte (CMs) production from hiPSCs, solely through small-molecule-based temporal modulation of the Wnt signalling, which generates more than 90% cTNT
cells. The impact of performing the differentiation process in 3D conditions as compared to a 2D culture system, was characterized by transcriptomic analysis by using data collected from sequential stages of 2D and 3D culture. We highlight that performing an initial period of hiPSC aggregation before cardiac differentiation primed hiPSCs towards an earlier mesendoderm lineage differentiation, via TGF-β/Nodal signaling stabilization. Importantly, it was also found that CMs in the 3D microenvironment mature earlier and show an improved communication system, which we suggested to be responsible for a higher structural and functional maturation of 3D cardiac aggregates.
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Human iPSC-derived self-organized cardiac tissues can be valuable for the development of platforms for disease modeling and drug screening, enhancing test accuracy and reducing pharmaceutical ...industry financial burden. However, current differentiation systems still rely on static culture conditions and specialized commercial microwells for aggregation, which hinders the full potential of hiPSC-derived cardiac tissues. Herein, we integrate cost-effective and reproducible manual aggregation of hiPSC-derived cardiac progenitors with Matrigel encapsulation and a dynamic culture to support hiPSC cardiac differentiation and self-organization. Manual aggregation at day 7 of cardiac differentiation resulted in 97% of beating aggregates with 78% of cTnT-positive cells. Matrigel encapsulation conjugated with a dynamic culture promoted cell migration and the creation of organized structures, with observed cell polarization and the creation of lumens. In addition, encapsulation increased buoyancy and decreased coalescence of the hiPSC-derived cardiac aggregates. Moreover, VEGF supplementation increased over two-fold the percentage of CD31-positive cells resulting in the emergence of microvessel-like structures. Thus, this study shows that the explored culture parameters support the self-organization of hiPSC-derived cardiac microtissues containing multiple cardiac cell types. Additional stimuli (e.g., BMP) in long-term scalable and fully automatized cultures can further potentiate highly structured and mature hiPSC-derived cardiac models, contributing to the development of reliable platforms for high-throughput drug screening and disease modeling.
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