Developing advanced organoids: challenges, progress, and outlook

BioTechniques, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: Jan. 29, 2025

Organoids, self-organizing 3D structures created from a variety of cell sources, offer unique advantages for studying organ development, modeling diseases, discovering new drugs, and creating regenerative therapies. However, their ability to completely mimic complex in vivo structure function has been hindered by the lack all relevant types found each organ; heterogeneity between organoids; variable reproducibility; mature phenotype; integrated neural, vascular, hematopoietic networks. To address these critical challenges, various strategies are being rapidly advanced include co-culturing co-differentiating multiple create region-and lineage-specific organoids together, including with vascular organoids, assembloids; using organoid-on-a-chip technology integrate perfusable vasculature within bioprinting organoids. This brief overview explores how converging disciplines stem biology, developmental bioengineering technologies have progressed creation increasingly sophisticated organoid models, provides an outlook on remaining challenges might be addressed.

Language: Английский

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Tackling pressure fluctuations in ultra-high performance liquid chromatography to robustly resolve and analyse polar metabolites

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108283 - 108283

Published: Feb. 1, 2025

The success of modern metabolomics analysis depends on the separation metabolites in complex samples using methods such as liquid chromatography and mass spectrometry. Herein, we present a protocol for resolving broad range polar metabolites, based hydrophilic interaction with zwitterionic bonded phase (HILICz). In optimising this protocol, encountered pressure fluctuations, widespread problem that impacts metabolite analysis, restricts batch sizes, imposes instrument downtime, ultimately incurring substantial time financial expense. Thus, use opportunity case study to demonstrate steps taken overcome resulting robustly consistently resolves large batches (>100 samples, equating >40 hours run-time). This consistency is essential address growing demand repeatable in-depth samples.

Language: Английский

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Engineered In Vitro Multi‐Cell Type Ventricle Model Generates Long‐Term Pulsatile Flow and Modulates Cardiac Output in Response to Cardioactive Drugs

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Cardiac in vitro models serve as promising platforms for physiological and pathological studies, drug testing, regenerative medicine. This study hypothesizes that immobilizing cardiomyocytes derived from human induced pluripotent stem cells (iPSC‐CMs) on a biofunctionalized, hemispherical membrane can generate pulsatile flow through synchronized contractions, thus offering an left ventricle model. To test this, using polydimethylsiloxane (PDMS) coated with polydopamine laminin 511 E8 fragments is engineered. Human iPSC‐CMs are cultured these membranes, alone or co‐culture cardiac fibroblasts endothelial cells, 28 14 days, respectively, newly developed bioreactor. Flow measurements track beating generation, while response, gene expression, cell morphology analyzed. The engineered ventricles maintain continuous flow, achieving theoretical output of up to 4 µL min −1 over indicating stable adhesion contraction. Cardiomyocytes respond cardioactive drugs (carbachol, isoproterenol) show expected changes heart rate output. In conclusion, the results demonstrate proposed model by supporting cardiomyocyte culture differentiation, generating long‐term responding physiologically drugs.

Language: Английский

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Three-Dimensional Magnetic Torque Stimulation Enhances Functional Structural Maturation in Developing Human Cardiac Organoids

Published: Jan. 1, 2025

Language: Английский

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Designing multicellular cardiac tissue engineering technologies for clinical translation

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 171, P. 103612 - 103612

Published: April 29, 2025

Cardiovascular diseases remain the leading cause of death worldwide-claiming one-third all deaths every year. Current two-dimensional in vitro cell culture systems and animal models cannot completely recapitulate clinical complexity these humans. Therefore, there is a dire need for higher fidelity biological capable replicating phenotypes to inform outcomes therapeutic development. Cardiac tissue engineering (CTE) strategies have emerged fulfill this by design three-dimensional myocardial from human pluripotent stem cells. In way, CTE serve as highly controllable variety applications-including physiological pathological modeling, drug discovery preclinical testing platforms, even direct interventions clinic. Although significant progress has been made development technologies, critical challenges necessary refinements are required derive more advanced heart technologies. review, we distill three focus areas field address: I) Generating cardiac muscle types scalable manufacturing methods, II) Engineering structure, function, analyses, III) Curating system specific application. each our areas, emphasize importance designing mimicking intricate intercellular connectivity discuss fundamental considerations that subsequently arise. We conclude highlighting cutting-edge applications use technologies modeling repair damaged diseased hearts.

Language: Английский

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