MAGIC matrices: freeform bioprinting materials to support complex and reproducible organoid morphogenesis DOI Creative Commons
Austin J. Graham, Michelle W.L. Khoo, Vasudha Srivastava

et al.

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

Published: Feb. 5, 2024

Organoids are powerful models of tissue physiology, yet their applications remain limited due to relatively simple morphology and high organoid-to-organoid structural variability. To address these limitations we developed a soft, composite yield-stress extracellular matrix that supports optimal organoid morphogenesis following freeform 3D bioprinting cell slurries at tissue-like densities. The material is designed with two temperature regimes: 4 °C it exhibits reversible behavior support long printing times without compromising viability. When transferred culture 37 °C, the cross-links similar viscoelasticity plasticity basement membrane extracts such as Matrigel. We first characterize rheological properties MAGIC matrices optimize morphogenesis, including low stiffness stress relaxation. Next, combine this custom piezoelectric printhead allows more reproducible robust self-organization from uniform spatially organized "seeds." apply for high-throughput generation intestinal, mammary, vascular, salivary gland, brain arrays structurally those grown in pure Matrigel, but exhibit dramatically improved homogeneity size, shape, maturation time, efficiency morphogenesis. flexibility method enabled fabrication fully microphysiological systems, perfusable tubes experience cyclic strain response pressurization. Furthermore, reproducibility structure increased statistical power drug assay by up 8 orders-of-magnitude given number comparisons. Combined, advances lay foundation efficient complex morphologies canalizing both space time.

Language: Английский

Landscape of human organoids: Ideal model in clinics and research DOI Creative Commons
Xinxin Han, Chunhui Cai, Wei Deng

et al.

The Innovation, Journal Year: 2024, Volume and Issue: 5(3), P. 100620 - 100620

Published: April 1, 2024

In the last decade, organoid research has entered a golden era, signifying pivotal shift in biomedical landscape. The year 2023 marked milestone with publication of thousands papers this arena, reflecting exponential growth. However, amid burgeoning expansion, comprehensive and accurate overview field been conspicuously absent. Our review is intended to bridge gap, providing panoramic view rapidly evolving We meticulously analyze from eight distinctive vantage points, harnessing our rich experience academic research, industrial application, clinical practice. present deep exploration advances technology, underpinned by long-standing involvement arena. narrative traverses historical genesis organoids their transformative impact across various sectors, including oncology, toxicology, drug development. delve into synergy between avant-garde technologies such as synthetic biology single-cell omics discuss role tailoring personalized medicine, enhancing high-throughput screening, constructing physiologically pertinent disease models. analysis reflective discourse provide dive existing landscape emerging trends technology. spotlight technological innovations, methodological evolution, broadening spectrum applications, emphasizing revolutionary influence discovery, other fields. Looking ahead, we cautiously anticipate future developments especially its potential implications for patient care, new avenues research. trust that will be an asset researchers, clinicians, patients keen interest medical strategies. offer broad prospective capabilities encompassing wide range current applications. summary, attempt field. reflections, summaries, projections might useful researchers hope contribute shaping trajectory dynamic advancing

Language: Английский

Citations

32
Precise and scalable self-organization in mammalian pseudo-embryos DOI
Mélody Merle,

Leah Friedman,

Corinne Chureau

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: 31(6), P. 896 - 902

Published: March 15, 2024

Language: Английский

Citations

21
Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids DOI Creative Commons
M Gerli, Giuseppe Calà, Max Arran Beesley

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 875 - 887

Published: March 1, 2024

Abstract Isolation of tissue-specific fetal stem cells and derivation primary organoids is limited to samples obtained from termination pregnancies, hampering prenatal investigation development congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation expansion during pregnancy, without the need for tissue or reprogramming, would be advantageous. Amniotic fluid (AF) a source multiple developing organs. Using single-cell analysis, we characterized cellular identities present human AF. We identified isolated viable epithelial stem/progenitor gastrointestinal, renal pulmonary origin. Upon culture, these formed clonal organoids, manifesting small intestine, kidney tubule lung identity. AF exhibit transcriptomic, protein expression functional features their With relevance disease modeling, derived tracheal diaphragmatic hernia fetuses, recapitulating some disease. timeline compatible with intervention, potentially allowing therapeutic tools regenerative medicine strategies personalized fetus at clinically relevant developmental stages.

Language: Английский

Citations

14
Humanized brain organoids-on-chip integrated with sensors for screening neuronal activity and neurotoxicity DOI
Pelin Sağlam-Metiner, Ender Yıldırım, Can Dincer

et al.

Microchimica Acta, Journal Year: 2024, Volume and Issue: 191(1)

Published: Jan. 1, 2024

Language: Английский

Citations

11
Immune cell-derived signals governing epithelial phenotypes in homeostasis and inflammation DOI Creative Commons
Annika Hausmann, Casper Steenholdt, Ole Haagen Nielsen

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 239 - 251

Published: Feb. 5, 2024

The intestinal epithelium fulfills important physiological functions and forms a physical barrier to the lumen. Barrier function is regulated by several pathways, its impairment contributes pathogenesis of inflammatory bowel disease (IBD), chronic condition affecting more than seven million people worldwide. Current treatment options specifically target mediators have led improvement clinical outcomes; however, significant proportion patients experience failure. Pro-repair effects on are emerging. In this review we summarize current knowledge involved epithelial identify open questions, put recent findings into perspective, pro-repair effects. A detailed understanding pathways integrating mucosal stimuli in homeostasis inflammation crucial for development novel, targeted therapies.

Language: Английский

Citations

10
Axially multifocal metalens for 3D volumetric photoacoustic imaging of neuromelanin in live brain organoid DOI Creative Commons
Aleksandr Barulin, Elena Barulina, Dong Kyo Oh

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(3)

Published: Jan. 15, 2025

Optical resolution photoacoustic imaging of uneven samples without z-scanning is transformative for the fast analysis and diagnosis diseases. However, current approaches to elongate depth field (DOF) typically imply cumbersome postprocessing procedures, bulky optical element ensembles, or substantial excitation beam side lobes. Metasurface technology allows phase modulation light miniaturization systems wavelength-size thickness. Here, we propose a metalens composed submicrometer-thick titanium oxide nanopillars, which generates an elongated diffraction-limited diameter with aspect ratio 286 uniform intensity throughout DOF. The enhances visualization phantom tilted surfaces compared conventional lenses. Moreover, volumetric neuromelanin facilitated depths up 500 micrometers within human midbrain forebrain organoids that are 3D biological models brain regions. This approach provides miniaturized platform neurodegenerative disease drug discovery.

Language: Английский

Citations

1
Integrated molecular-phenotypic profiling reveals metabolic control of morphological variation in a stem-cell-based embryo model DOI Creative Commons

Alba Villaronga-Luque,

Ryan Savill, Natalia López-Anguita

et al.

Cell stem cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic remain unclear. Here, we investigated roots by parallel recording transcriptomic states morphological history individual structures modeling embryonic trunk formation. Machine learning integration time-resolved single-cell RNA sequencing with imaging-based profiling identified early features predictive end states. Leveraging power revealed that imbalance oxidative phosphorylation glycolysis results aberrant morphology a neural lineage bias, which confirmed metabolic measurements. Accordingly, interventions improved Collectively, our work establishes divergent as drivers offers broadly applicable framework to chart predict organoids SEMs. strategy can be used identify control underlying processes, ultimately increasing reproducibility.

Language: Английский

Citations

1
Transforming Toxicity Assessment through Microphysiology, Bioprinting, and Computational Modeling DOI Open Access

Tamer A. Addissouky

Advances in Clinical Toxicology, Journal Year: 2024, Volume and Issue: 9(1), P. 1 - 14

Published: Jan. 1, 2024

Background: Traditional toxicity testing emphasizes animal models with growing concerns regarding predictive capacity, throughput and ethics. Rapid innovation surrounding human cell platforms, bioengineered tissues, omics techniques computational tools offers more modern alternatives aligned expanding knowledge of chemical biological pathways. These disruptive approaches promise immense potential to transform next-generation safety assessment drug development pipelines. Purpose: This review provides clinical researchers an updated, comprehensive perspective across evolving areas focus in new methods analysis latest advances translational context. Main Body: We survey progress two- three-dimensional cultures recapitulating tissue/organ complexity impossible conventional assays. Complementing this, modeling integrates structure-activity relationships, physicochemical properties physiological interactions predict pharmacokinetics silico. Expanding model organisms add further dimensionality demographic relevance. High-throughput imaging technologies unravel mechanisms illuminate biomarkers undetectable by standard measures. Specialized show high addressing toxicodynamic intricacies within disease contexts like diabetes NAFLD. Evaluating traditional medicines phytochemicals likewise represents area growth well-suited for contemporary platforms. Future outlook weighs remarkable advantages reducing demands, enabling precision toxicology links medicine overhauling core risk frameworks. Conclusion: intends catalyze discourse on strategic optimization priorities roadmaps towards fully unlocking the yet still emerging public health these poising transformation sciences centered human-focused models.

Language: Английский

Citations

6
Organoids as regenerative medicine for inflammatory bowel disease DOI Creative Commons
Alexander Hammerhøj,

Deepavali Chakravarti,

Toshiro Sato

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 110118 - 110118

Published: May 27, 2024

Inflammatory bowel disease (IBD) is a chronic disorder with an increasing global prevalence. Managing activity relies on various pharmacological options. However, the effectiveness of current therapeutics limited and not universally applicable to all patients circumstances. Consequently, developing new management strategies necessary. Recent advances in endoscopically obtained intestinal biopsy specimens have highlighted potential epithelial organoid transplantation as novel therapeutic approach. Experimental studies using murine human transplantations shown promising outcomes, including tissue regeneration functional recovery. Human trials therapy commenced; thus, this article provides readers insights into necessity regenerative option clinical settings explores its associated challenges.

Language: Английский

Citations

5
Standardization and consensus in the development and application of bone organoids DOI Creative Commons
Wang Jian, Xiao Chen, Ruiyang Li

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 15(2), P. 682 - 706

Published: Dec. 2, 2024

Organoids, self-organized structures derived from stem cells cultured in a specific three-dimensional (3D) vitro microenvironment, have emerged as innovative platforms that closely mimic vivo cellular behavior, tissue architecture, and organ function. Bone organoids, frontier organoid research, can replicate the complex functional characteristics of bone tissue. Recent advancements led to successful development including models callus, woven bone, cartilage, trabecular marrow. These organoids are widely utilized establishing bone-related disease models, injury repair, drug screening. However, significant discrepancies remain between current human skeletal tissues terms morphology functionality, limiting their ability accurately model physiology pathology. To address these challenges promote standardization construction, evaluation, application we convened experts research teams with substantial expertise field. By integrating existing findings, this consortium aims establish consensus guide future organoids.

Language: Английский

Citations

5