Inner Ear Organoids: Recent Progress and Potential Applications DOI Creative Commons
Yiyun Lou, Yaoqian Liu, Mingxuan Wu

et al.

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

Conditional Overexpression of Serpine2 Promotes Hair Cell Regeneration from Lgr5+ Progenitors in the Neonatal Mouse Cochlea DOI Creative Commons

Hairong Xiao,

Jiheng Wu,

Lixuan Huang

et al.

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

Published: March 17, 2025

Abstract Neonatal cochlear Lgr5+ progenitors retain limited hair cells (HCs) regenerative capacity, but the regulatory network remains incompletely defined. Serpin family E member 2 ( Serpine2 ) is shown to participate in regulating proliferation and differentiation of previous vitro study. Here, expression pattern vivo roles HC regeneration are explored by transgenic mice. It found that expressed mouse cochlea after birth with a downward trend as mice age. In addition, conditional overexpression neonatal results an increased number ectopic HCs dose‐dependent manner. knockdown ex can inhibit regeneration. EdU assay lineage tracing demonstrate these likely originate from through direct transdifferentiation rather than mitotic Moreover, single‐nucleus RNA sequencing analysis mRNA level validation reveal conditionally overexpressed induces via inhibiting sonic hedgehog (SHH) signal pathway inducing Atoh1 Pou4f3 transcription factor. brief, data indicate plays pivotal role cochlea, this suggests new avenue for future research into

Language: Английский

Citations

1
Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell–like cells in adult mice DOI Creative Commons

Yizhou Quan,

Wei Wei, Volkan Ergin

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(17)

Published: April 17, 2023

Strategies to overcome irreversible cochlear hair cell (HC) damage and loss in mammals are of vital importance hearing recovery patients with permanent loss. In mature mammalian cochlea, co-activation Myc Notch1 reprograms supporting cells (SC) promotes HC regeneration. Understanding the underlying mechanisms may aid development a clinically relevant approach achieve regeneration nontransgenic cochlea. By single-cell RNAseq, we show that MYC/NICD “rejuvenates” adult mouse cochlea by activating multiple pathways including Wnt cyclase activator cyclic AMP (cAMP), whose blockade suppresses HC-like despite / Notch activation. We screened identified combination (the cocktail) drug-like molecules composing small interfering RNAs activate Myc, Notch1, cAMP. cocktail effectively replaces transgenes fully wild-type (WT) SCs for vitro. Finally, demonstrate is capable reprogramming WT mice vivo. Our study identifies strategy reprogram inner ear regeneration, laying foundation restoration

Language: Английский

Citations

21
Stem Cell-Based Hair Cell Regeneration and Therapy in the Inner Ear DOI Creative Commons
Jieyu Qi, Wenjuan Huang,

Yicheng Lu

et al.

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(1), P. 113 - 126

Published: Oct. 3, 2023

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible of hair cells is a main cause sensorineural hearing loss, currently, only relatively effective clinical treatments are limited to digital equipment like cochlear implants aids, but these benefit in patients. It therefore urgent understand mechanisms damage repair order develop new neuroprotective strategies. At present, how promote regeneration functional key scientific question field research. Multiple signaling pathways transcriptional factors trigger activation cell progenitors ensure maturation newborn cells, this article, we first review principal underlying reproduction. We then further discuss therapeutic strategies involving co-regulation multiple induce after degeneration, summarize current achievements regeneration. Lastly, potential future approaches, such as small molecule drugs gene therapy, which might be applied for regenerating clinic.

Language: Английский

Citations

19
Hair Cell Regeneration: From Animals to Humans DOI Creative Commons
Sung‐Won Choi, Julia M. Abitbol, Alan G. Cheng

et al.

Clinical and Experimental Otorhinolaryngology, Journal Year: 2024, Volume and Issue: 17(1), P. 1 - 14

Published: Jan. 19, 2024

Cochlear hair cells convert sound into electrical signals that are relayed via the spiral ganglion neurons to central auditory pathway. Hair vulnerable damage caused by excessive noise, aging, and ototoxic agents. Non-mammals can regenerate lost mitotic regeneration direct transdifferentiation of surrounding supporting cells. However, in mature mammals, damaged not replaced, resulting permanent hearing loss. Recent studies have uncovered mechanisms which sensory organs non-mammals neonatal mammalian cochlea cells, outlined possible why this ability declines rapidly with age mammals. Here, we review similarities differences between avian, zebrafish, cell regeneration. Moreover, discuss advances limitations their potential applications human

Language: Английский

Citations

8
GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways DOI Creative Commons
Fei Tan, Xuran Li, Li Xiao

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 95 - 95

Published: Jan. 11, 2024

Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, which the patient has intact low-frequency hearing and profound high-frequency pre-operatively. Therefore, synergistic restoration of dysfunctional hair cells protection from ototoxic insults have become a persistent target pursued for this hybrid system. In study, we developed composite GelMA/PEDOT:PSS conductive hydrogel that is suitable coating implant electrode potential local delivery otoregenerative otoprotective drugs. Various material characterization methods (e.g., 1H NMR spectroscopy, FT-IR, EIS, SEM), experimental models murine organoid aminoglycoside-induced HEI-OC1 cellular model), biological analyses confocal laser scanning microscopy, real time qPCR, flow cytometry, bioinformatic sequencing) were used. The results demonstrated decent properties hydrogel, mechanical high tensile stress Young’s modulus), electrochemical low impedance conductivity), biocompatibility satisfactory cell interaction free systemic toxicity), biosafety minimal hemolysis death) features. addition, CDR medicinal cocktail sustainably released not only promoted expansion stem but also boosted trans-differentiation supporting into cells. Furthermore, hydrogel-based drug protected oxidative various forms programmed death apoptosis ferroptosis). Finally, using large-scale sequencing, enriched complex network signaling pathways potentially downstream to metabolic processes abundant metabolites. conclusion, present bifunctional cocktails, thereby serving solution intracochlear therapy auditory rehabilitation diseases beyond.

Language: Английский

Citations

7
An atlas of neuropathic pain-associated molecular pathological characteristics in the mouse spinal cord DOI Creative Commons
Fulu Dong, Lina Yu,

Pei-Da Feng

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 17, 2025

Peripheral nerve injury (PNI)-induced neuropathic pain (NP) is a severe disease with high prevalence in clinics. Gene reprogramming and tissue remodeling the dorsal root ganglia (DRG) spinal cord (SC) drive development maintenance of (NP). However, our understanding NP-associated spatial molecular processing landscape SC non-synaptic interactions between DRG neurons cells remains limited. We here integrate transcriptomics (ST) single-nucleus RNA-sequencing (snRNA-seq) bulk (bulk RNA-seq) to characterize regional pathological heterogeneity under NP conditions. First, mice manifests unique atlases genes, cell populations, cell-cell cross-talks, signaling pathways, transcriptional regulatory networks compared sham mice. further report that injured sensory corresponding ventral horn show similar expression patterns after PNI. In addition, for first time, we systematically exhibit "cross-talk omics" glial cells, indicating an altered communication profile Together, findings decode cellular mechanisms underlying NP, providing foundation designing therapeutic targets this disorder.

Language: Английский

Citations

1
Extracellular vesicles for developing targeted hearing loss therapy DOI

Xiaoshu Pan,

Yanjun Li, Peixin Huang

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 366, P. 460 - 478

Published: Jan. 11, 2024

Language: Английский

Citations

6
MEK/ERK signaling drives the transdifferentiation of supporting cells into functional hair cells by modulating the Notch pathway DOI Creative Commons
Jiaoyao Ma, Mingyu Xia, Jin Guo

et al.

Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: 13(7), P. 661 - 677

Published: May 6, 2024

Abstract Loss of cochlear hair cells (HCs) leads to permanent hearing loss in mammals, and regenerative medicine is regarded as an ideal strategy for recovery. Limited genetic pharmaceutical approaches HC regeneration have been established, the existing strategies cannot achieve recovery auditory function. A promising target promote MEK/ERK signaling because dynamic shifts its activity during critical stages inner ear development observed. Here, we first showed that activated specifically supporting (SCs) after aminoglycoside-induced injury. We then selected 4 inhibitors, PD0325901 (PD03) was found induce transdifferentiation functional supernumerary HCs from SCs neonatal mammalian epithelium. next PD03 facilitated generation organoids. Through genome-wide high-throughput RNA sequencing verification, Notch pathway downstream signaling. Importantly, delivery into induced mild vivo. Our study thus reveals importance cell fate determination suggests might serve a new approach regeneration.

Language: Английский

Citations

5
Magnetic/Acoustic Dual‐Controlled Microrobot Overcoming Oto‐Biological Barrier for On‐Demand Multidrug Delivery against Hearing Loss DOI
Xinyang Yi,

Lifang Guo,

Qi Zeng

et al.

Small, Journal Year: 2024, Volume and Issue: 20(44)

Published: July 17, 2024

Multidrug combination therapy in the inner ear faces diverse challenges due to distinct physicochemical properties of drugs and difficulties overcoming oto-biologic barrier. Although nanomedicine platforms offer potential solutions multidrug delivery, access remains limited. Micro/nanomachines, capable delivering cargo actively, are promising tools for bio-barriers. Herein, a novel microrobot-based strategy penetrate round window membrane (RWM) is presented on-demand manner delivered. The tube-type microrobot (TTMR) constructed using template-assisted layer-by-layer (LbL) assembly chitosan/ferroferric oxide/silicon dioxide (CS/Fe

Language: Английский

Citations

5
Recent advances in molecular studies on cochlear development and regeneration DOI
Yuwei Sun, Zhiyong Liu

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102745 - 102745

Published: June 24, 2023

Language: Английский

Citations

11