Generation of vascularized brain organoids to study neurovascular interactions

eLife, Journal Year: 2022, Volume and Issue: 11

Published: May 4, 2022

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, lack vasculatures, which regulate neurogenesis disorders, limits utility organoids. In this study, we induced vessel organoids, respectively, then fused two types together obtain vascularized The were engrafted with robust vascular network-like structures exhibited increased number neural progenitors, in line possibility that vessels development. Fusion also contained functional blood–brain barrier-like structures, as well microglial cells, a specific population immune cells brain. incorporated microglia responded actively stimuli showed ability engulfing synapses. Thus, fusion established study allow modeling interactions between neuronal non-neuronal components vitro, particularly vasculature niche.

Language: Английский

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Advancing cell therapy for neurodegenerative diseases

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 512 - 529

Published: April 20, 2023

Language: Английский

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Blood Vessel Organoids for Development and Disease

Circulation Research, Journal Year: 2023, Volume and Issue: 132(4), P. 498 - 510

Published: Feb. 16, 2023

Despite enormous advances, cardiovascular disorders are still a major threat to global health and responsible for one-third of deaths worldwide. Research new therapeutics the investigation their effects on vascular parameters is often limited by species-specific pathways lack high-throughput methods. The complex 3-dimensional environment blood vessels, intricate cellular crosstalks, organ-specific architectures further complicate quest faithful human in vitro model. development novel organoid models various tissues such as brain, gut, kidney signified leap field personalized medicine disease research. By utilizing either embryonic- or patient-derived stem cells, different developmental pathological mechanisms can be modeled investigated controlled environment. We have recently developed self-organizing capillary vessel organoids that recapitulate key processes vasculogenesis, angiogenesis, diabetic vasculopathy. Since then, this system has been utilized model other processes, refined, adapted organ specificity. In review, we will discuss alternative approaches engineering explore identity engineered vessels comparison vivo vasculature. Future perspectives therapeutic potential discussed.

Language: Английский

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Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(6), P. 818 - 833.e11

Published: May 15, 2024

Language: Английский

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Landscape of human organoids: Ideal model in clinics and research

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

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Bioengineering methods for vascularizing organoids

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(6), P. 100779 - 100779

Published: May 16, 2024

Organoids, self-organizing three-dimensional (3D) structures derived from stem cells, offer unique advantages for studying organ development, modeling diseases, and screening potential therapeutics. However, their translational ability to mimic complex in vivo functions are often hindered by the lack of an integrated vascular network. To address this critical limitation, bioengineering strategies rapidly advancing enable efficient vascularization organoids. These methods encompass co-culturing organoids with various cell types, lineage-specific organoids, co-differentiating cells into organ-specific lineages, using organoid-on-a-chip technology integrate perfusable vasculature within 3D bioprinting also create This review explores field organoid vascularization, examining biological principles that inform approaches. Additionally, envisions how converging disciplines biology, biomaterials, advanced fabrication technologies will propel creation increasingly sophisticated models, ultimately accelerating biomedical discoveries innovations.

Language: Английский

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The Promise and Potential of Brain Organoids

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: Jan. 22, 2024

Brain organoids are 3D in vitro culture systems derived from human pluripotent stem cells that self-organize to model features of the (developing) brain. This review examines techniques behind organoid generation, their current and potential applications, future directions for field. possess complex architecture containing various neural cell types, synapses, myelination. They have been utilized toxicology testing, disease modeling, infection studies, personalized medicine, gene-environment interaction studies. An emerging concept termed Organoid Intelligence (OI) combines with artificial intelligence generate learning memory, goals modeling cognition enabling biological computing applications. allow neuroscience studies not previously achievable traditional techniques, transform drug development, understanding brain development disorders. The aspirational vision OI parallels origins intelligence, efforts underway map a roadmap toward its realization. In summary, constitute disruptive technology is rapidly advancing gaining traction across multiple disciplines.

Language: Английский

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Vascularized human brain organoids: current possibilities and prospects

Trends in biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Human brain organoids (hBOs) are in vitro, 3D, self-organizing tissue structures increasingly used for modeling development and disease. Although they traditionally lack vasculature, recent bioengineering developments enable their vascularization, which partly recapitulates neurodevelopmental processes such as neural tube angiogenesis, formation of neurovascular unit (NVU)-like structures, early barriergenesis. vascularized hBOs (vhBOs) already to model (defects in) development, vascularization efficiency other outcomes differ substantially between protocols overall shortcomings should be considered. For instance, vessel-like vhBOs do not contain blood-like flow nor form a functional blood-brain barrier (BBB). Extended characterization, standardization, the new techniques may broader applications drug transport studies.

Language: Английский

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High‐Throughput Formation of Pre‐Vascularized hiPSC‐Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Abstract Liver organoids have been increasingly adopted as a critical in vitro model to study liver development and diseases. However, the pre‐vascularization of without affecting parenchymal specification remains long‐lasting challenge, which is essential for their application regenerative medicine. Here, large‐scale formation pre‐vascularized human hepatobiliary (vhHBOs) presented epithelial via novel strategy, namely nonparenchymal cell grafting (NCG). Endothelial mesenchymal cells are grafted (hHBOs) at different differentiation stages supplementing with culture medium growth factors. stage hepatic maturation offers an optimal integration efficiency compared specification. Additionally, proves crucial endothelial invading sprouting into during establishment vhHBOs. Ectopic implants mice further displayed vhHBOs vascular networks. Notably, transplanted self‐organized native tissue like zone bile ducts, indicating potential regenerate damaged duct tissues. It believed that will offer technical route form high‐fidelity complex engineering

Language: Английский

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Human assembloids

Development, Journal Year: 2022, Volume and Issue: 149(20)

Published: Oct. 15, 2022

ABSTRACT Deconstructing and then reconstructing developmental processes ex vivo is crucial to understanding how organs assemble physiology can be disrupted in disease. Human 3D stem cell-derived systems, such as organoids, have facilitated this pursuit; however, they often do not capture inter-tissue or inter-lineage cellular interactions that give rise emergent tissue properties during development. Assembloids are self-organizing systems result from the integration of multiple organoids combination with missing cell types primary explants. Here, we outline concept assembloids present their applications for studying nervous system other tissues. We describe tools used probe manipulate delineate current challenges potential new approach interrogate development

Language: Английский

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