Validation of microphysiological systems for interpreting patient heterogeneity requires robust reproducibility analytics and experimental metadata

Cell Reports Methods, Journal Year: 2025, Volume and Issue: unknown, P. 101028 - 101028

Published: April 1, 2025

Multi-cell-type, 3D microphysiological systems (MPS) that recapitulate normal organ/organ system functions and the progression of diseases are being applied in drug discovery development programs to enable precision medicine. A critical step for this application is demonstrate reproducibility MPS its ability identify biologic/clinical heterogeneity from experimental variability, which requires capturing detailed metadata associated with studies as well a strong analytical approach assessing reproducibility. Detailed ensure identical study parameters compared when evaluating We have developed Pittsburgh protocol (PReP), uses set common statistical metrics, coefficient variation (CV), ANOVA, intraclass correlation (ICC), pipeline standard evaluate intra- interstudy performance. The PReP can be employed biological/clinical relevant

Language: Английский

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Latest Advanced Techniques for Improving Intestinal Organoids Limitations

Stem Cell Reviews and Reports, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Language: Английский

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What public health challenges and unmet medical needs would benefit from interdisciplinary collaboration in the EU? A survey and multi-stakeholder debate

Frontiers in Public Health, Journal Year: 2024, Volume and Issue: 12

Published: July 22, 2024

In the past decade, significant European calls for research proposals have supported translational collaborative on non-communicable and infectious diseases within biomedical life sciences by bringing together interdisciplinary multinational consortia. This has advanced our understanding of disease pathophysiology, marking considerable scientific progress. Yet, it is crucial to retrospectively evaluate these efforts' societal impact. Research should be thoughtfully designed ensure that findings can effectively translated into actionable policies. addition, choice methods plays a pivotal role in shaping impact discoveries. Understanding factors responsible current unmet public health issues medical needs crafting innovative strategies policy interventions. A multistakeholder survey roundtable helped identify potential consideration EU agenda. Based findings, mental disorders, metabolic syndrome, cancer, antimicrobial resistance, environmental pollution, cardiovascular were considered challenges deserving prioritisation. early diagnosis, primary prevention, pollution onset personalised medicine approaches most selected needs. Survey enabled formulation some research-policies interventions (RPIs), which further discussed during online roundtable. The discussion underscored recent EU-level activities aligned with survey-derived RPIs facilitated an exchange perspectives topics ripe collaboration warranting attention EU's Actionable recommendations aimed at facilitating translation knowledge transformative, science-based policies are also provided.

Language: Английский

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On-Chip NADH Detection in Multicellular Models Using an AlGaN/GaN Photodetector Array with Enhanced Sensitivity

Nano Letters, Journal Year: 2024, Volume and Issue: 24(47), P. 14993 - 15000

Published: Oct. 30, 2024

Nicotinamide adenine dinucleotide (NAD) is a pivotal coenzyme, existing in its oxidized form (NAD

Language: Английский

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Arrested Coalescence: A Tool to Explore Tissue Rheology

Biophysica, Journal Year: 2024, Volume and Issue: 4(4), P. 604 - 618

Published: Nov. 28, 2024

Tissue spheroids are self-organised 3D cellular aggregates that serve as a versatile platform in tissue engineering. While numerous high-throughput methods exist to characterise the function of spheroids, equivalent techniques for mechanical characterisation still lacking. In this review, we focus on fusion— simple, fast, and inexpensive method rheology spheroids. We begin by discussing implications development disease, followed detailed explanation how phenomenon arrested coalescence can be used explore Finally, present different theoretical models that, when combined with experimental data, allow us extract rheological information.

Language: Английский

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Histone Trimethylations and HDAC5 Regulate Spheroid Subpopulation and Differentiation Signaling of Human Adipose-Derived Stem Cells

Stem Cells Translational Medicine, Journal Year: 2023, Volume and Issue: 13(3), P. 293 - 308

Published: Dec. 30, 2023

Human adipose-derived stem cells (ASCs) have shown immense potential for regenerative medicine. Our previous work demonstrated that chitosan nano-deposited surfaces induce spheroid formation and differentiation of ASCs treating sciatic nerve injuries. However, the underlying cell fate mechanisms ASC-derived spheroids remain unknown. Here, we investigate epigenetic regulation signaling coordination these therapeutic spheroids. During formation, observed significant increases in histone 3 trimethylation at lysine 4 (H3K4me3), 9 (H3K9me3), 27 (H3K27me3), accompanied by increased deacetylase (HDAC) activities decreased acetyltransferase activities. Additionally, HDAC5 translocated from cytoplasm to nucleus, along with nuclear Utilizing single-cell RNA sequencing (scRNA-seq), analyzed chitosan-induced ASC discovered distinct cluster subpopulations, trajectories, traits, networks using 10x Genomics platform, R studio/language, Ingenuity Pathway Analysis (IPA) tool. Specific subpopulations were identified within corresponded a transient reprogramming state (Cluster 6) endpoint 3). H3K4me3 H3K9me3 as key regulators IPA initiate Cluster 6 cells, confirmed qPCR their respective methyltransferase inhibitors: SNDX-5613 (a KMT2A inhibitor H3K4me3) SUVi (an SUV39H1 H3K9me3). Moreover, involved regulating downstream neuronal markers during cells. These findings emphasize critical role regulation, particularly H3K4me3, H3K9me3, HDAC5, shaping directing lineage-specific differentiation.

Language: Английский

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Tumor Organoid as a Drug Screening Platform for Cancer Research

Current Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 19(9), P. 1210 - 1250

Published: Oct. 15, 2023

A number of studies have been conducted on the application 3D models for drug discovery, sensitivity assessment, and toxicity. Most these focused disease modelling attempted to control cellular differentiation, heterogeneity, key physiological features mimic organ reconstitution so that researchers could achieve an accurate response in evaluation. Recently, organoids used by various scientists due their highly organotypic structure, which facilitates translation from basic research clinic, especially cancer research. With this tool, can perform high-throughput analyses compounds determine exact effect patients based genetic variations, as well develop personalized combination therapies. Although there is a lack standardization organoid culture, patientderived (PDOs) become widely established testing. In review, we discussed recent advances tumoroids not only screening but also clinical trials demonstrate potential translational medicine.

Language: Английский

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Modelling phenotypes, variants and pathomechanisms of syndromic diseases in different systems

Medizinische Genetik, Journal Year: 2024, Volume and Issue: 36(2), P. 121 - 131

Published: June 5, 2024

Language: Английский

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Enhanced Mitochondrial Function and Delivery from Adipose-Derived Stem Cell Spheres via the EZH2-H3K27me3-PPARγ Pathway for Advanced Therapy

Published: Oct. 21, 2024

Background Microenvironmental alterations induce significant genetic and epigenetic changes in stem cells. Mitochondria, essential for regenerative capabilities, provide the necessary energy cell function. However, specific roles of histone modifications mitochondrial dynamics human adipose-derived cells (ASCs) during morphological transformations remain poorly understood. In this study, we aim to elucidate mechanisms by which ASC sphere formation enhances function, delivery, rescue efficiency. Methods ASCs were cultured on chitosan nano-deposited surfaces form 3D spheres. Mitochondrial activity ATP production assessed using MitoTracker staining, Seahorse XF analysis, luminescence assays. Single-cell RNA sequencing, followed Ingenuity Pathway Analysis (IPA), was conducted uncover key regulatory pathways, validated through molecular techniques. involvement confirmed inhibitors or PPARγ-modulating drugs. structural integrity delivery efficiency evaluated after isolation. Results Chitosan-induced spheres exhibited unique compact morphology, characterized condensed cristae, enhanced activity, increased oxidative phosphorylation. High expressions complex I genes elevated levels proteins observed without an increase reactive oxygen species (ROS). Epigenetic modification H3K27me3 PPARγ discovered inhibiting with EZH2 inhibitor GSK126 adding agonist Rosiglitazone (RSG). Isolated mitochondria from showed improved stability efficiency, suppressed inflammatory cytokines LPS- TNFα-induced inflamed cells, rescued damage, thereby enhancing function promoting recovery. Conclusion Enhancing via EZH2-H3K27me3-PPARγ pathway offers alternative strategy conventional cell-based therapies. High-functional show potential medicine applications.

Language: Английский

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The YTHDF Proteins Shape the Brain Gene Signatures of Alzheimer's Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Summary The gene signatures of Alzheimer’s Disease (AD) brains reflect an output a complex interplay genetic, epigenetic, epi-transcriptomic, and post-transcriptional regulations. To identify the most significant factor that shapes AD brain signature, we developed machine learning model (DEcode-tree) to integrate cellular molecular factors explaining differential expression in AD. Our indicates YTHDF proteins, canonical readers N6-methyladenosine RNA modification (m6A), are influential predictors signature. We then show protein modules containing YTHDFs downregulated human brains, knocking out iPSC-derived neural cells recapitulates signature vitro . Furthermore, eCLIP-seq analysis revealed proteins influence through both m6A-dependent independent pathways. These results indicate central role shaping brains.

Language: Английский

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