Vascularized human brain organoids: current possibilities and prospects

Trends in biotechnology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

---

A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in cortical organoids

iScience, Год журнала: 2025, Номер 28(2), С. 111853 - 111853

Опубликована: Янв. 21, 2025

Язык: Английский

---

Morphogenesis and development of human telencephalic organoids in the absence and presence of exogenous extracellular matrix

The EMBO Journal, Год журнала: 2023, Номер 42(22)

Опубликована: Окт. 16, 2023

The establishment and maintenance of apical-basal polarity is a fundamental step in brain development, instructing the organization neural progenitor cells (NPCs) developing cerebral cortex. Particularly, basally located extracellular matrix (ECM) crucial for this process. In vitro, epithelial polarization can be achieved via endogenous ECM production, or exogenous supplementation. While neuroepithelial development recapitulated organoids, effects different sources tissue morphogenesis remain underexplored. Here, we show that exposure to solubilized basement membrane substrate, Matrigel, at early stages causes rapid rearrangement architecture. cultures exposed pure components unexposed any ECM, acquisition slower driven by production. After onset neurogenesis, architecture neuronal differentiation are largely independent initial source, but Matrigel has long-lasting on patterning. These results advance knowledge mechanisms exogenously endogenously guided morphogenesis, demonstrating self-sustainability processes.

Язык: Английский

---

Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 28, 2023

Abstract Pluripotent stem cell (PSC)-derived human brain organoids enable the study of development in vitro. Typically, fate PSCs is guided into subsequent specification steps through static medium switches. In vivo, morphogen gradients are critical for proper and determine specification, associated defects result neurodevelopmental disorders. Here, we show that initiating neural induction a temporal stepwise gradient guides generation composed single, self-organized apical-out neuroepithelium, termed ENOs (expanded neuroepithelium organoids). This at odds with standard organoid protocols which multiple independent units (rosettes) formed. We find prolonged, decreasing TGF-β signaling determining factor ENO formation allows an extended phase expansion. In-depth characterization reveals display improved cellular morphology tissue architectural features resemble vivo development, including expanded germinal zones. Consequently, cortical enhanced ENOs. constitute platform to early events allow interrogation complex relationship between architecture states shaping developing brain.

Язык: Английский

---

Brain organoid protocols and limitations

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 20, 2024

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends scope our understanding human biology diseases. Brain organoids especially open an opportunity for brain modeling many neurological diseases, which have lagged due to inaccessibility samples lack similarity with other animal models. can be generated through various protocols mimic whole or region-specific. To provide overview technology, we summarize currently available list several factors consider before choosing protocols. We also outline limitations current challenges need solved in future investigation development pathobiology.

Язык: Английский

---

Rigor and reproducibility in human brain organoid research: Where we are and where we need to go

Stem Cell Reports, Год журнала: 2024, Номер 19(6), С. 796 - 816

Опубликована: Май 16, 2024

Human brain organoid models have emerged as a promising tool for studying human development and function. These preserve genetics recapitulate some aspects of development, while facilitating manipulation in an vitro setting. Despite their potential to transform biology medicine, concerns persist about fidelity. To fully harness potential, it is imperative establish reliable analytic methods, ensuring rigor reproducibility. Here, we review current analytical platforms used characterize forebrain cortical organoids, highlight challenges, propose recommendations future studies achieve greater precision uniformity across laboratories.

Язык: Английский

---

ARID1B controls transcriptional programs of axon projection in an organoid model of the human corpus callosum

Cell stem cell, Год журнала: 2024, Номер 31(6), С. 866 - 885.e14

Опубликована: Май 7, 2024

Mutations in ARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms humans. The most common structural abnormality brain ARID1B patients is agenesis corpus callosum (ACC), characterized by absence an interhemispheric white matter tract that connects distant cortical regions. Here, we find neurons expressing SATB2, determinant callosal projection neuron (CPN) identity, show impaired maturation ARID1B+/− neural organoids. Molecularly, reduction chromatin accessibility genomic regions targeted TCF-like, NFI-like, and ARID-like transcription factors drives differential expression genes required for (CC) development. Through vitro model CC tract, demonstrate this transcriptional dysregulation impairs formation long-range axonal projections, causing underconnectivity. Our study uncovers new functions during human corticogenesis, identifying cell-autonomous axonogenesis defects SATB2+ as ACC patients.

Язык: Английский

---

Modelling human brain development and disease with organoids

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 12, 2024

Язык: Английский

---

Microfibrous Scaffolds Guide Stem Cell Lumenogenesis and Brain Organoid Engineering

Advanced Materials, Год журнала: 2023, Номер 35(41)

Опубликована: Авг. 12, 2023

3D organoids are widely used as tractable in vitro models capable of elucidating aspects human development and disease. However, the manual low-throughput culture methods, coupled with a low reproducibility geometric heterogeneity, restrict scope application organoid research. Combining expertise from stem cell biology bioengineering offers promising approach to address some these limitations. Here, melt electrospinning writing is generate tuneable grid scaffolds that can guide self-organization pluripotent cells into patterned arrays embryoid bodies. Grid geometry shown be key determinant self-organization, guiding position size emerging lumens via curvature-controlled tissue growth. Two distinct methods for culturing scaffold-grown bodies either interconnected or spatially discrete cerebral reported. These provide high-throughput method generate, culture, analyze large numbers organoids, substantially reducing time investment labor involved conventional culture. It anticipated this methodological will open up new opportunities studying lumenogenesis, generating uniform screening.

Язык: Английский

---

Complex in vitro models positioned for impact to drug testing in pharma: a review

Biofabrication, Год журнала: 2024, Номер 16(4), С. 042006 - 042006

Опубликована: Авг. 27, 2024

Abstract Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids organs-on-chip, a technology with potential to reduce animal usage pharma while also enhancing our ability create safe efficacious drugs for patients. Public awareness CIVMs has increased, part, due recent passage FDA Modernization Act 2.0. This visibility is expected spur deeper investment adoption models. Thus, end-users model developers alike require framework both understand readiness current enter drug development process, assess upcoming same. review presents selection based on comparative -omics data (which we term model-omics), metrics qualification specific test assays that may support context-of-use (COU) assays. We surveyed existing healthy tissue ten development-critical organs body, provide evaluations suggestions improving model-omics COU each. In whole, this comes from perspective, seeks an evaluation where are poised maximum impact roadmap realizing potential.

Язык: Английский

---