Bioengineered skin organoids: from development to applications

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: Aug. 22, 2023

Abstract Significant advancements have been made in recent years the development of highly sophisticated skin organoids. Serving as three-dimensional models that mimic human skin, these organoids evolved into complex structures and are increasingly recognized effective alternatives to traditional culture due their ability overcome limitations two-dimensional systems ethical concerns. The inherent plasticity allows for construction physiological pathological models, enabling study dynamic changes. This review provides an overview pivotal work progression from 3D layered epidermis cyst-like with appendages. Furthermore, it highlights latest organoid facilitated by state-of-the-art engineering techniques, such printing microfluidic devices. also summarizes discusses diverse applications developmental biology, disease modelling, regenerative medicine, personalized while considering prospects limitations.

Language: Английский

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Varying mechanical forces drive sensory epithelium formation

Science Advances, Journal Year: 2023, Volume and Issue: 9(44)

Published: Nov. 3, 2023

The mechanical cues of the external microenvironment have been recognized as essential clues driving cell behavior. Although intracellular signals modulating fate during sensory epithelium development is well understood, force formation remains elusive. Here, we manufactured a hybrid hydrogel with tunable properties for cochlear organoids culture and revealed that extracellular matrix (ECM) drives through shifting stiffness in stage-dependent pattern. As force, moderate ECM activated expansion progenitor (CPC)–derived epithelial by integrin α3 (ITGA3)/F-actin cytoskeleton/YAP signaling. Higher induced transition CPCs into hair cells (HCs) increasing Ca 2+ signaling mediated PIEZO2 then activating KLF2 to accomplish specification . Our results identify molecular mechanism guided contribute developing therapeutic approaches HC regeneration.

Language: Английский

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Cell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(20)

Published: May 26, 2023

Abstract With the advent of mechanobiology, cell shape and forces have emerged as essential elements behavior fate, in addition to biochemical factors such growth factors. Cell are intrinsically linked physical properties environment. Extracellular stiffness guides migration single cells collectives well differentiation developmental processes. In confined environments, division patterns altered, death or extrusion might be initiated, other modes become possible. Tools from materials science adhesive micropatterning soft elastic substrates direct laser writing 3D scaffolds been established control quantify structured environments. Herein, a review is given on recent experimental modeling advances this field, which currently moves tissue. A very exciting avenue combination organoids with because will allow one achieve organotypic function controlled setting suited for long‐term high‐throughput culture.

Language: Английский

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Epithelial UNC-23 limits mechanical stress to maintain glia-neuron architecture in C. elegans

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(13), P. 1668 - 1688.e7

Published: April 25, 2024

For an organ to maintain correct architecture and function, its diverse cellular components must coordinate their size shape. Although cell-intrinsic mechanisms driving homotypic cell-cell coordination are known, it is unclear how cell shape regulated across heterotypic cells. We find that epithelial cells the of neighboring sense-organ glia-neuron units in adult Caenorhabditis elegans (C. elegans). Hsp co-chaperone UNC-23/BAG2 prevents from deforming, loss causes head epithelia stretch aberrantly during animal movement. In glia, amphid sheath (AMsh), this progressive fibroblast growth factor receptor (FGFR)-dependent disruption glial apical cytoskeleton. Resultant alteration concomitant change glia-associated neuron endings. Epithelial UNC-23 maintenance specific both spatially, within a defined anatomical zone, temporally, developmentally critical period. As all molecular uncovered broadly conserved central peripheral nervous systems, we posit may similarly regulate cross-species.

Language: Английский

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Chemically defined and dynamic click hydrogels support hair cell differentiation in human inner ear organoids

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102386 - 102386

Published: Jan. 1, 2025

Highlights•Multifunctional, dynamic hydrogels display highly tunable mechanical properties•Gel stiffness influences inner ear organoid viability and otic vesicle formation•Dynamic permit the generation of authentic progenitor cells•Encapsulated progenitors give rise to later-stage cell populationsSummaryThe properties in microenvironment play a key role its patterning during embryonic development. To recapitulate development vitro, three-dimensional tissue engineering strategies including application representative models scaffolds are increasing interest. Human organoids promising model developmental processes; however, current protocol requires Matrigel that contains ill-defined extracellular matrix components. Here, we implement an alternative, chemically defined, hydrogel support differentiation human organoids. Specifically, thiol-norbornene hydrazide-aldehyde click chemistries used fabricate organoid-laden, gelatin-based scaffolds. We identify optimal formulations hair with comparable efficiency fidelity Matrigel-cultured These results suggest defined may serve as viable alternative for engineering.Graphical abstract

Language: Английский

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Apical expansion of calvarial osteoblasts and suture patency is dependent on fibronectin cues

Development, Journal Year: 2024, Volume and Issue: 151(7)

Published: April 1, 2024

ABSTRACT The skull roof, or calvaria, is comprised of interlocking plates bones that encase the brain. Separating these are fibrous sutures permit growth. Currently, we do not understand instructions for directional growth a process which error-prone and can lead to skeletal deficiencies premature suture fusion (craniosynostosis, CS). Here, identify graded expression fibronectin (FN1) in mouse embryonic cranial mesenchyme (CM) precedes apical expansion calvaria. Conditional deletion Fn1 Wasl leads diminished frontal bone by altering cell shape focal actin enrichment, respectively, suggesting defective migration calvarial progenitors. Interestingly, mutants have coronal sutures. Consistently, syndromic forms CS humans exhibit dysregulated FN1 expression, also find altered model Apert syndrome. These data support as substrate osteoblast may be common mechanism underlying many disorders disparate genetic etiologies.

Language: Английский

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Advancements in inner ear development, regeneration, and repair through otic organoids

Current Opinion in Genetics & Development, Journal Year: 2022, Volume and Issue: 76, P. 101954 - 101954

Published: July 16, 2022

The vertebrate inner ear contains a diversity of unique cell types arranged in particularly complex 3D cytoarchitecture. Both these features are integral to the proper development, function, and maintenance hearing balance. Since elucidation timing delivery signaling molecules produce sensory cells, supporting neurons from human induced pluripotent stem we have entered revolution using organ-like ‘otic organoid’ cultures explore specific genetic programs, developmental rules, potential therapeutics. This review aims highlight selection reviews primary research papers past two years particular merit that use otic organoids investigate broadly defined topics reprogramming, regeneration, repair.

Language: Английский

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Inner Ear Organoids: Recent Progress and Potential Applications

Fundamental Research, Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 1, 2023

The inner ear is one of the most complicated structures that harbor organs for perception sound and balance, which deep in temporal bone challenging to operate. Organoids serve as promising platforms understanding developmental processes pathological dysfunctions discovering therapeutic drugs gene therapy strategies disorders ear. To better understand origin application value organoids, we reviewed history advancement organoid research. We summarized cell sources organoids matrices supporting their formation. research on derived from pluripotent stem cells (PSCs) primary progenitor has been clarified detail. elaborated applications development, hereditary deafness modeling, hair (HC) regeneration strategy formulation. Finally, mentioned limitations current culture methods described several prospects optimizing next-generation potential translational applications.

Language: Английский

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Epithelia delimits glial apical polarity against mechanical shear to maintain glia-neuron - architecture

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Dec. 27, 2022

ABSTRACT For an organ to maintain proper architecture and function, its different component cell-types must coordinate their cell-shapes with each other through life. While cell-intrinsic developmental mechanisms driving homotypic cell-cell coordination are known, how heterotypic cells collectively regulate cell-shape is less-clear. We report that, in a sense-organ, epithelial delimit polarity domains of contacting glia, thereby, associated neuron shapes throughout Briefly, Hsp co-chaperone UNC-23/BAG2 keeps apical from deforming animal movement. Epithelial stretch aberrantly progressively adult unc-23 mutant animals, which FGFR-dependent manner, dislocates glial cytoskeleton proteins SMA-1/β H -Spectrin actin. This alters cell shape, concomitantly, neuron-ending shape. Notably, UNC-23 acts temporally at critical period glia-neuron shape adults, spatially within defined anatomical zone. Lastly, intervention either epithelia, glia or ameliorate phenocopy neural defects. Epi/endothelia resist mechanical stress contact units across central/peripheral nervous systems species, all components the identified molecular pathway conserved disease-relevant. Thus, we posit that analogous epithelia-glia mechanobiological coupling may broadly

Language: Английский

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Apical expansion of calvarial osteoblasts and suture patency is dependent on graded fibronectin cues

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 16, 2023

The skull roof, or calvaria, is comprised of interlocking plates bone. Premature suture fusion (craniosynostosis, CS) persistent fontanelles are common defects in calvarial development. Although some the genetic causes these disorders known, we lack an understanding instructions directing growth and migration progenitors bones, which may affect patency. Here, identify graded expression Fibronectin (FN1) protein mouse embryonic cranial mesenchyme (CM) that precedes apical expansion osteoblasts. Syndromic forms CS exhibit dysregulated FN1 expression, find altered a model as well. Conditional deletion

Language: Английский

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