Organoids as an Emerging Tool for Nano-Pharmaceuticals
Harishkumar Madhyastha, Durgesh Nandini Chauhan in 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).
3D In Vitro/Ex Vivo Systems
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Three-dimensional hydrogel systems have emerged as a model for drug delivery and treatment of diseases related to the lung. More specifically, these systems are utilizing organoids which are 3D developing tissues that provide researchers with an accurate representation of microanatomy (Fang and Eglen 2017). Figure 29.1 shows the overall scheme for developing organoid tissues. Organoids are essentially a collection of cell types that are specific to the organ of interest. Organoids are typically formed from stem cells and organize into the cell type in a manner similar to this process in vivo. Also, tissue organoids are cultured as being mesenchyme-free. These cells are most commonly studied in the lung because they directly apply to epithelial cells due to their capabilities to organize into structures resembling this tissue. Current researchers are using these in vivo organoid models to resemble the lung tissue microanatomy and environment. As a result, these models accurately demonstrate the impact of certain drugs on lung tissue. Furthermore, all of these qualities and characteristics of multi-dimensional hydrogels provide researchers with the ability to culture different cell types in the same environment to gain a complete understanding of their interactions.
Modelling human neurodegeneration using induced pluripotent stem cells
Christine Hauskeller, Arne Manzeschke, Anja Pichl in The Matrix of Stem Cell Research, 2019
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).
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.
Brain Models in a Dish: Ethical Issues in Developing Brain Organoids
Published in AJOB Neuroscience, 2019
The potential benefits of this research include helping to illuminate early brain development and providing a better understanding of neurodevelopmental disorders such as autism, Alzheimer’s disease, and schizophrenia. Genetic disorders can be modeled through using patient-derived induced pluripotent stem cells from patients suffering from the problem. Additionally, organoids that model disease can be used for drug testing in place of animal studies and may better recapitulate the effects of the drugs in human patients (Lancaster and Knoblich 2014, 283). In the case of brain research, these models are likely to provide a more accurate representation of normal and abnormal human brain function than animal models. One group of researchers commenting on the ethics of experimenting with human brain organoids wrote that “the promise of brain surrogates is such that abandoning them seems itself unethical, given the vast amount of human suffering caused by neurological disorders” (Farahany et al. 2018, 429).
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].
Related Knowledge Centers
- Embryoid Body
- Embryonic Stem Cell
- In Vitro
- Induced Pluripotent Stem Cell
- Tissue
- Cellular Differentiation
- Stem Cell
- Cell
- Differential Adhesion Hypothesis
- Teratoma