Modern In Vitro Techniques for Modeling Hearing Loss DOI Creative Commons
Jamie J. Shah,

Couger A. Jimenez-Jaramillo,

Zane R. Lybrand

et al.

Bioengineering, Journal Year: 2024, Volume and Issue: 11(5), P. 425 - 425

Published: April 26, 2024

Sensorineural hearing loss (SNHL) is a prevalent and growing global health concern, especially within operational medicine, with limited therapeutic options available. This review article explores the emerging field of in vitro otic organoids as promising platform for modeling developing novel strategies. SNHL primarily results from irreversible or dysfunction cochlear mechanosensory hair cells (HCs) spiral ganglion neurons (SGNs), emphasizing need innovative solutions. Current interventions offer symptomatic relief but do not address root causes. Otic organoids, three-dimensional multicellular constructs that mimic inner ear’s architecture, have shown immense potential several critical areas. They enable testing gene therapies, drug discovery sensory cell regeneration, study ear development pathology. Unlike traditional animal models, closely replicate human pathophysiology, making them invaluable translational research. discusses methodological advances organoid generation, use pluripotent stem (hPSCs) to development. Cellular molecular characterization efforts identified key markers pathways essential development, shedding light on their disorders. Technological innovations, such 3D bioprinting microfluidics, further enhanced fidelity these models. Despite challenges limitations, including standardized protocols ethical considerations, transformative approach understanding treating auditory dysfunctions. As this matures, it holds revolutionize treatment landscape balance disorders, moving us closer personalized medicine conditions.

Language: Английский

PKM2 controls cochlear development through lactate-dependent transcriptional regulation DOI Creative Commons

Mingxuan Wu,

Gaogan Jia,

Yaoqian Liu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(2)

Published: Jan. 8, 2025

Understanding the role of metabolic processes during inner ear development is essential for identifying targets hair cell (HC) regeneration, as choices play a crucial in proliferation and differentiation. Among processes, growing evidence shows that glucose metabolism closely related to organ development. However, mammalian HC regeneration remains unclear. In this study, we found glycolytic highly active mouse human cochlear prosensory epithelium expansion. Using organoids, revealed activity nonsensory epithelial cells was predominantly dominated by pyruvate kinase M2 (PKM2). Deletion PKM2 induced switch from glycolysis oxidative phosphorylation, impairing organoid formation. Furthermore, conditional loss progenitors hindered sensory morphogenesis, demonstrated knockout mice. Mechanistically, generated catalysis then converted into lactate, which lactylates histone H3, regulating transcription key genes Specifically, accumulated lactate causes H3 lactylation at lysine 9 (H3K9la), upregulating expression Sox family factors through epigenetic modification. Moreover, overexpression supporting (SCs) triggered reprogramming enhanced generation cultured explants. Our findings uncover molecular mechanism formation driven glycolysis-lactate flow suggest unique approaches regeneration.

Language: Английский

Citations

2
Varying mechanical forces drive sensory epithelium formation DOI Creative Commons
Mingyu Xia, Mingxuan Wu,

Yuanrong Li

et al.

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

Citations

24
Organoid-guided precision hepatology for metabolic liver disease DOI
Sho Osonoi, Takanori Takebe

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 80(5), P. 805 - 821

Published: Jan. 17, 2024

Language: Английский

Citations

11
Regulatory mechanisms of connexin26 DOI
Ya Ke, Xiaozhou Liu, Yu Sun

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Modeling, applications and challenges of inner ear organoid DOI Creative Commons
Jieyu Qi, Liyan Zhang, Xiaohan Wang

et al.

Smart Medicine, Journal Year: 2024, Volume and Issue: 3(1)

Published: Jan. 16, 2024

More than 6% of the world's population is suffering from hearing loss and balance disorders. The inner ear organ that senses sound balance. Although disorders are common, there limited ways to intervene restore its sensory functions. development establishment biologically therapeutic interventions for auditory require clarification basics signaling pathways control endogenous or exogenous cell-based methods. In vitro models ear, such as organoid systems, can help identify new protective regenerative drugs, develop gene therapies, be considered potential tools future clinical applications. Advances in stem cell technology culture offer unique opportunities modeling diseases developing personalized therapies loss. Here, we review discuss mechanisms applications organoids.

Language: Английский

Citations

6
Integration of Functional Human Auditory Neural Circuits Based on a 3D Carbon Nanotube System DOI Creative Commons
Yiyun Lou, Jiaoyao Ma, Yangnan Hu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 18, 2024

Abstract The physiological interactions between the peripheral and central auditory systems are crucial for information transmission perception, while reliable models neural circuits currently lacking. To address this issue, mouse human pathways generated by utilizing a carbon nanotube nanofiber system. super‐aligned pattern of scaffold renders axons bipolar multipolar neurons extending in parallel direction. In addition, electrical conductivity maintains electrophysiological activity primary neurons. from units system then co‐cultured showed that two kinds form synaptic connections. Moreover, progenitor cells cochlea cortex derived embryos to generate region‐specific organoids these assembled nanofiber‐combined 3D Using optogenetic stimulation, calcium imaging, recording, it is revealed functional connections formed neurons, as evidenced spiking postsynaptic currents. circuit model will enable study pathway advance search treatment strategies disorders neuronal connectivity sensorineural hearing loss.

Language: Английский

Citations

5
Current advances in biomaterials for inner ear cell regeneration DOI Creative Commons
Junze Lu, Man Wang, Yu Meng

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 12, 2024

Inner ear cell regeneration from stem/progenitor cells provides potential therapeutic strategies for the restoration of sensorineural hearing loss (SNHL), however, efficiency is low and functions differentiated are not yet mature. Biomaterials have been used in inner to construct a more physiologically relevant 3D culture system which mimics stem microenvironment facilitates cellular interactions. Currently, these biomaterials include hydrogel, conductive materials, magneto-responsive photo-responsive etc. We analyzed characteristics described advantages limitations materials. Furthermore, we reviewed mechanisms by with different physicochemical properties act on depicted current status material selection based their achieve reconstruction auditory circuits. The application offers promising opportunities circuits hearing, should be strategically explored combined according obstacles solved research.

Language: Английский

Citations

4
Metabolic Profiling of Cochlear Organoids Identifies α‐Ketoglutarate and NAD+ as Limiting Factors for Hair Cell Reprogramming DOI Creative Commons
Qing Liu, Linqing Zhang, Zhen Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 11, 2024

Cochlear hair cells are the sensory responsible for transduction of acoustic signals. In mammals, damaged do not regenerate, resulting in permanent hearing loss. Reprogramming surrounding supporting to functional represent a novel strategy restoration. However, cellular processes governing efficient and cell reprogramming completely understood. Employing mouse cochlear organoid system, detailed metabolomic characterizations expanding differentiating organoids performed. It is found that differentiation associated with increased mitochondrial electron transport chain (ETC) activity reactive oxidative species generation. Transcriptome metabolome analyses indicate reduced expression oxidoreductases tricyclic acid (TCA) cycle metabolites. The metabolic decoupling between ETC TCA limits availability key cofactors, α-ketoglutarate (α-KG) nicotinamide adenine dinucleotide (NAD

Language: Английский

Citations

3
Recent Progress in Generation of Inner Ear Organoid DOI

Yanjun Zong,

Xiaozhou Liu,

Yaqi Zhang

et al.

Advanced Biology, Journal Year: 2024, Volume and Issue: 8(10)

Published: July 25, 2024

Abstract Inner ear organoids play a crucial role in hearing research. In comparison to other animal models and 2D cell culture systems, inner offer significant advantages for studying the mechanisms of development exploring novel approaches disease treatment. derived from human cells are more closely resemble normal organs function. The 3D system organoid enhances cell–cell interactions mimics internal environment. this review, progress limitations methods tissue‐specific progenitors pluripotent stem (PSCs) summarized, which may new insights into generating that terms morphology

Language: Английский

Citations

1
Timing and Graded BMP Signalling Determines Fate of Neural Crest and Ectodermal Placode Derivatives from Pluripotent Stem Cells DOI Creative Commons

Keshi Chung,

M. F. Millet,

Ludivine Rouillon

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2262 - 2262

Published: Oct. 4, 2024

Pluripotent stem cells (PSCs) offer many potential research and clinical benefits due to their ability differentiate into nearly every cell type in the body. They are often used as model systems study early stages of ontogenesis better understand key developmental pathways, well for drug screening. However, order fully realise PSCs translational applications, a deeper understanding especially humans, is required. Several signalling molecules play important roles during development required proper differentiation PSCs. The concentration timing signal activation important, with perturbations resulting improper and/or pathology. Bone morphogenetic proteins (BMPs) one such group involved specification various types tissues human body, including those related tooth otic development. In this review, we describe role BMP its regulation, consequences dysregulation disease differentiation, how can be investigate effects modulation development, mainly focusing on Finally, emphasise unique BMP4 refined controlling regulation could lead generation more robust reproducible PSC-derived organoids applications.

Language: Английский

Citations

1