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Organoids as an Emerging Tool for Nano-Pharmaceuticals
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Organoids are stem cell-derived, three-dimensional (3D) cultured structures that are generated ex-vivo. Mostly, organoids are composed of distinct types of cells that are derived from organ progenitors or pluripotent stem cells (Lancaster and Knoblich 2014). Over a period of time, advancement in technology to differentiate stem cells and drive them into specific lineages has revolutionised the field of three-dimensional models of development. Moreover, these developments helped in disease modelling, which led to the elucidation of etiologic pathways involved in human pathologies. Another important angle in organoid culture is the use of biomaterials to include the effect of all surrounding microenvironment and thus gives an opportunity to explore the purpose of various cues in the determination of cell fate. Specifically, mechanical perturbations imposed by entropy and dynamic turbulences in tissue/3D organoid systems play critical regulatory roles.
Next Generation Tissue Engineering Strategies by Combination of Organoid Formation and 3D Bioprinting
Published in Naznin Sultana, Sanchita Bandyopadhyay-Ghosh, Chin Fhong Soon, Tissue Engineering Strategies for Organ Regeneration, 2020
Shikha Chawla, Juhi Chakraborty, Sourabh Ghosh
Despite these fascinating prospects offered by the field of organoid development, this field of research suffers from many limitations. Firstly, to replicate the dynamic and complex course of in vivo like spatio-temporal delivery of cytokine/morphogens in these 3D organoids is still an unachievable goal. Secondly, mostly organoids are made up of only few thousand cells. These organoids offer limited control over dimensional and structural features of the individual tissue/ organ; even if larger organoids are developed, there are limitations with respect to supply of nutrients and oxygen (Gjorevski et al. 2014). Thus, there is a need for combinatorial bioengineering methodologies that can narrow down the discontinuity between in vitro organoid based tissue culture models and in vivo morphogenesis. Such combinatorial approaches have the potential to deduce the complex mechanistic insight about developmental organogenesis thus opening new avenues for drug discovery and rapid drug testing. In future probably, tissue engineers will be able to generate new strategies for tissue regeneration in the clinic using such culture technologies.
Microarray 3D Bioprinting for Creating Miniature Human Tissue Replicas for Predictive Compound Screening
Published in Hyun Jung Kim, Biomimetic Microengineering, 2020
Alexander D. Roth, Stephen Hong, Moo-Yeal Lee
Recent advances in organoid cultures, including the brain, heart, lung, liver, intestine, and pancreas, have demonstrated great promise as human tissue replicas. They can mimic morphological features of human tissues and contain multiple cell types relevant to specific tissues in vivo, maintaining viability and function for several weeks (Picollet-D’hahan et al. 2017). While organoids represent a new direction in predictive in vitro efficacy and toxicity screening, there are several technical challenges to adopt organoids in disease modeling (Laurent et al. 2017). Current organoid cultures rely on the ability of pluripotent stem cells (PSCs) to self-organize into discrete tissue structures with a step-wise process that mimics normal organ development (McCauley and Wells 2017). This spontaneous differentiation of PSCs into multiple cell lineages, as well as clone-dependent differences, determines the structural complexity and cell-type diversity in organoids, leading to considerable organoid variations (Ranga, Gjorevski, and Lutolf 2014; Gjorevski, Ranga, and Lutolf 2014).
Large three-dimensional cell constructs for tissue engineering
Published in Science and Technology of Advanced Materials, 2021
Jun-Ichi Sasaki, Gabriela L Abe, Aonan Li, Takuya Matsumoto, Satoshi Imazato
The term organoid is interpreted as a 3D artificial organ produced in vitro [101–103]. Bone- and dental pulp-like tissues fabricated from 3D cell constructs are also categorized into the organoids. Recently, there has been an increase in organoid research and technologies using laminated cell sheets and a 3D bioprinter was established for in vitro tissue engineering [104–107]. Notably, the advantages of 3D cell constructs are 1) that they are easy to control the size (>10 mm) and morphology, 2) their simple construction, 3) their high biosafety and biocompatibility without a scaffold, and 4) their ability to reproduce the biomimetic environment because of their self-organizing ability. Therefore, it is considered that organ-like biomaterials originating from a 3D cell construct are applicable to pharmaceutical science and developmental biology as well as regenerative medicine. Meanwhile, tissue defects can often involve extremely large areas and various specialized tissues at once. These conditions remain a challenge to cell construct application given the great number of cells necessary to promote defect reconstitution. Nonetheless, iPS cells may represent an unlimited source of stem cells, which could be adopted to fabricate cell constructs of extreme sizes. This idea would benefit from further investigation on size and morphology, utilizing iPS cells as resource, and improving on the suitability of 3D cell construct for applications.
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Maria João Bessa, Fátima Brandão, Fernanda Rosário, Luciana Moreira, Ana Teresa Reis, Vanessa Valdiglesias, Blanca Laffon, Sónia Fraga, João Paulo Teixeira
Spheroids and organoids are 3D structures composed of multiple cells that cluster together into self-organized aggregates. Both terms are often used interchangeably in the literature, though some differences exist between the two. Spheroids are simple spherical and scaffold-free cellular models that are typically obtained from mature single-cell suspensions (Zanoni et al. 2020). On the other hand, organoids are complex clusters derived from organ-specific cells that self-assemble within a scaffold such as gels made of a complex mixture of different extracellular matrix (ECM) proteins, including laminin, fibronectin, collagen, and heparin sulfate (e.g., Matrigel), though not all organoids are formed within an ECM (Gkatzis et al. 2018). Organoids may be generated from adult or embryonic stem cells (Hofer and Lutolf 2021). One curious aspect of these particular 3D structures is that they can be maintained for prolonged periods of time without karyotype changes (Kar et al. 2021). In the respiratory field, organoids are valuable models to mimic the complex environment of the respiratory mucosa and the relationship between different cell types. Indeed, human lung organoids have been successfully established from cells of different origins such as epithelial progenitor cells derived from embryonic (Miller et al. 2018) or adult lung (Tan et al. 2017; Zacharias et al. 2018), and from human pluripotent stem cells (hPSC) (Chen et al. 2017; Gotoh et al. 2014; Yamamoto et al. 2017). Previously, establishment of alveolar organoids from cocultures of epithelial progenitor cells with mesenchymal or endothelial cells or from cocultures of mesenchymal cells with fetal lung tissue or hPSC were reported (Wilkinson et al. 2016).