Opportunities of patient‐derived organoids in drug development

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Various model systems are utilised during drug development starting from basic research, moving to preclinical research and for clinical applications in order identify new drugs improve human health. However, there characteristics of humans that not captured by established models. Such models include homogeneous two‐dimensional (2D) cell lines, which lack cellular heterogeneity physiological relevance, species differences animal Organoids can mitigate these providing more physiologically relevant three‐dimensional (3D) resemble the molecular state healthy pathological tissue. This review presents exemplary approaches using patient‐derived organoids (PDOs) have been developed opportunities evolving with a focus on patient adult stem (ASC)‐derived organoids. These demonstrate potential PDOs used alongside such as personalised medicine.

Language: Английский

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Standards for Organoids

International Journal of Stem Cells, Journal Year: 2024, Volume and Issue: 17(2), P. 99 - 101

Published: May 27, 2024

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Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Oct. 23, 2024

One of the critical processes in human reproduction that is still poorly understood implantation. The implantation an early embryo considered a significant limitation successful pregnancy. Therefore, researchers are trying to develop ideal model endometrium vitro can mimic endometrial micro-environment vivo as much possible. ultimate goal modeling study molecular interactions at embryo-maternal interface and use this diagnostic tool for infertility. Significant progress has been made over years generating such models. first experiments involved animal models, which undoubtedly valuable, but same time, their dissimilarities with tissue represent obstacle further research. This fact led basic monolayer coculture systems using uterine cells obtained from biopsies and, later on, complex multilayer With engineering methods various cultivation systems, it possible form two-dimensional (2D) models three-dimensional (3D) organoids novel assembloids recapitulate many aspects architecture cell composition. These have already helped provide new insight into embryo-endometrium interplay. main aim paper comprehensive review past current approaches generation, feasibility, potential clinical application infertility treatment.

Language: Английский

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TGFβ2‐Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Abstract Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron‐dependent regulated cell death, as a central mechanism driving salivary gland (SG) dysfunction. In OVX‐SGs, TGFβ signaling pathway is enhanced with aberrant TGFβ2 expression SG mesenchymal cells. Intriguingly, treatment reduces iron‐storing ferritin levels, leading to lipid peroxidation ferroptotic death epithelial organoids (SGOs). Mechanistically, promotes autophagy‐mediated degradation, so‐called ferritinophagy. A notable overexpression type III receptor (TβRIII) found OVX‐SGs TGFβ2‐treated SGOs, while silencing TβRIII mitigates ferroptosis‐mediated deleterious effects on SGOs. Finally, administration ferroptosis inhibitor, Liproxstatin‐1 (Lip‐1), improves saliva secretion OVX mice. Present findings collectively suggest link between signaling, injury, offering new avenues for xerostomia.

Language: Английский

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Revolutionising oral organoids with artificial intelligence.

PubMed, Journal Year: 2024, Volume and Issue: 5(4), P. 372 - 389

Published: Jan. 1, 2024

The convergence of organoid technology and artificial intelligence (AI) is poised to revolutionise oral healthcare. Organoids - three-dimensional structures derived from human tissues offer invaluable insights into the complex biology diseases, allowing researchers effectively study disease mechanisms test therapeutic interventions in environments that closely mimic vivo conditions. In this review, we first present historical development organoids delve current types organoids, focusing on their use models, regeneration microbiome intervention. We then compare single-source multi-lineage assess latest progress bioprinted, vascularised neural-integrated organoids. next part highlight significant advancements AI, emphasising how AI algorithms may potentially promote for early detection diagnosis, personalised treatment, prediction drug screening. However, our main finding identification remaining challenges, such as data integration critical need rigorous validation ensure clinical reliability. Our viewpoint AI-enabled are still limited applications but, look future, potential transformation AI-integrated microbial interactions discoveries. By synthesising these components, review aims provide a comprehensive perspective state future implications role advancing healthcare improving patient outcomes.

Language: Английский

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