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Organoids as an Emerging Tool for Nano-Pharmaceuticals
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Developing novel drugs (drug discovery) and identifying novel therapeutic molecular targets is a long, costly, and challenging task because of limited success in the initial screening process at the in vitro level. As a result, there have been significant advancements towards adopting more biomimetic platforms for drug screening platforms with higher fidelity for testing bioactivity and toxicity. To this end, in recent years, there have been encouraging efforts towards switching from 2D assays to physiologically more acceptable 3D system of assays, including cell-based assays and multicellular spheroid models as well miniaturised organ on chip systems (Ranga et al. 2016). In particular, in last few years, there have been consistent attempts to develop complex multicellular constructs termed “Organoid” equivalents for organs towards providing high-value de-risking platforms for recapitulating properties of respective organs. These 3D assays can potentially fill the gap and connect the missing link between primary drug screening of compounds and forward lead optimisation into animal and human clinical trials (Figure 7.3).
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
The most interesting application of these organoids is possibly the design and development of in vitro disease model systems, degenerative conditions, developmental disease and tumors (Clevers 2016). Furthermore, in future such in vitro organoid models may offer additional prospect to derive tissue/mini-organs from patient’s own cells to provide substitute to organ replacement (Lancaster and Knoblich 2014).
Modelling human neurodegeneration using induced pluripotent stem cells
Published in Christine Hauskeller, Arne Manzeschke, Anja Pichl, The Matrix of Stem Cell Research, 2019
Iryna Prots, Beate Winner, Jürgen Winkler
As stated above, significant discoveries of disease-causing and disease-driving mechanisms have been made in neurons obtained from patient-specific iPSC. It is however important to note that neurons, even being disease-specific, might behave differently in a dish in contrast to a diseased environment, such as the brain tissue of a patient with neurodegenerative disease. This could limit the wide extrapolation of the results obtained with iPSC-derived cells. To overcome these difficulties, scientists have begun to produce iPSC-derived three-dimensional models of specialized tissues, called organoids, which have key features of their counterparts in a living organism. Organoids are useful systems for investigating a cell in a physiological and/or diseased surrounding. For example, cerebral organoids called ‘mini brains’ have been used to model the complex neurodevelopmental disorder microcephaly that causes abnormal growth of the brain (Clevers, 2016).
3D bioprinting for organ and organoid models and disease modeling
Published in Expert Opinion on Drug Discovery, 2023
Amanda C. Juraski, Sonali Sharma, Sydney Sparanese, Victor A. da Silva, Julie Wong, Zachary Laksman, Ryan Flannigan, Leili Rohani, Stephanie M. Willerth
As mentioned in section 1.1, many innovative drugs and therapies for CNS diseases do not reach the market due to off-target effects or excessive toxicity Almost 90% of investigated drugs fail along the clinical research process, in great part due to the inadequacies of current in vitro models [15,20]. The use of organoids offers the possibility to rule out drugs with undesired effects or without clinical relevance in a more timely and commercially competitive way. Therefore, 3D bioprinted tissue models such as organoids could offer a standard tool for reliable results on the necessary outputs for drug screening models. Sharma et al. (2020) bioprinted brain organoids using a fibrin-based bioink and neuro progenitor cells (NPCs) from hiPSCs and microspheres loaded with the anti-cancer drug guggulsterone. Both loaded and control constructs presented high cell viability, with more than 90% of viable cells up to a week after printing. The microspheres-loaded constructs presented a 92% cell viability one day after the bioprinting and it increased to 98% 7 days post-printing. Drug loading also affected cell differentiation. While all constructs expressed TUJ1 (cell marker for immature neurons) and FOXA2 (marker for midbrain-type dopaminergic neurons), only guggulsterone-loaded organoids expressed tyrosine hydroxalase (TH – an enzyme expressed by dopaminergic neurons), suggesting that the delivery of guggulsterone by the microspheres helped to direct the stem cells into neuronal differentiation [63].
The application of pancreatic cancer organoids for novel drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Michael Karl Melzer, Yazid Resheq, Fatemeh Navaee, Alexander Kleger
Of note, organoids appear to compete with several other established methods in personalized medicine. These methods include the application of genomics in PDAC to identify druggable mutations [111] for patients who do not respond to approved treatments, e.g. the application of sotorasib for the KRASG12C mutation [9]. Although less commonly applied in PDAC, a liquid biopsy may provide a readily accessible and cost-efficient platform for early diagnosis of PDAC, capturing mutational patterns, and monitoring therapy response [112] in the future. Nevertheless, organoids have a major advantage over the techniques mentioned above as they faithfully recapitulate dynamic in-vivo-processes in vitro. This recapitulation is likely to become even more sophisticated with novel culture techniques such as microchips or the construction of assembloids. Thus, organoids may complement or be combined with the methods above to achieve comprehensive, personalized medicine, where the advantages of several approaches merge.
Novel hydrogels: are they poised to transform 3D cell-based assay systems in early drug discovery?
Published in Expert Opinion on Drug Discovery, 2023
J. Mark Treherne, Aline F. Miller
In contrast, an organoid is a generic term typically used to define a simplified version of an organ, or tissue, that is produced in a 3D environment. Here, it self-assembles in vitro to form a realistic microanatomy, such as a spherical intestinal-like structure [18]. Organoids are derived from one or a few cells from a tissue sample containing adult or embryonic stem cells. Alternatively, they are grown from induced pluripotent stem cells (iPSCs), which then self-organize in culture, resulting from their self-renewal and cellular differentiation properties. Organoids are not grown in a typical 2D format but are seeded and maintained in 3D for the entirety of that passage in hydrogels. The techniques for growing organoids reliably have improved in recent years and Nature Methods selected organoid culture as their Method of the Year for 2017 [19]. Recent advances have enabled the long-term growth of organoids which opens up their scientific potential as research tools for screening assays [19]. Typically, organoid systems are more complex, or advanced than spheroids. Consequently, they are increasingly being used not only in basic research, such as in developmental biology studies, but also in commercial drug discovery applications [3]. Organoids are typically required to be grown in hydrogels to mimic exogenous ECM.