Magnetic stem cell targeting to the inner ear

Le, Trung; Straatman, Louise V.; Yanai, Anat; Rahmanian, Ronak; Garnis, Cathie; Häfeli, Urs O.; Poblete, T.; Westerberg, Brian D.; Gregory-Evans, Kevin

doi:10.1016/j.jmmm.2017.07.033

Cited by 14 publications

(12 citation statements)

References 79 publications

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“…Cochlear regeneration does not occur spontaneously. However, stem cell therapy suggests that repair and replacement of lost hair cells may be possible (Bermingham‐Mcdonogh & Rubel, ; Le et al, ; Parker & Cotanche, ; Schomann et al, ). Baicalin can promote neuron development, improve memory and learning impairment induced by the injury of brain in mammals, and enhances Schwann cell viability by regulating neurotrophic factors in vitro (Matsui & Cotanche, ; Smith et al, ; Zuo et al, ).…”

Section: Discussionmentioning

confidence: 99%

Baicalin attenuates gentamicin‐induced cochlear hair cell ototoxicity

Xian-fen

2019

J of Applied Toxicology

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Gentamicin can lead to cochlear hair cells associated ototoxicity by inducing apoptosis and oxidative stress, which can be alleviated by baicalin, one flavonoid extracted from the root of Scutellaria baicalensis. The role of baicalin in protecting gentamicin-induced hearing loss is unclear. Interference with oxidative stress was investigated in this study using House Ear Institute-Organ of Corti1 (HEI-OC1) cells, which were simultaneously treated with baicalin (0-400 μM) and gentamicin (0.2 or 1 mM). MTT was used to assay cell viability and apoptosis was detected with Annexin V-fluorescein isothiocyanate staining. The production of reactive oxygen species was indicated by 2,7-dichlorofluorescein diacetate fluorescence intensity and mitochondrial depolarization was assayed by JC1-mitochondrial membrane potential assay. Poly(ADP-ribose) polymerase (PARP), cleaved-caspase 3 and cleaved-PARP expression were analyzed with western blot. Baicalin improved the viability of HEI-OC1 cells and significantly reduced the oxidative stress and mitochondrial depolarization compared with the gentamicin treatment group. Gentamicin treatment increased the activation of PARP and caspase-3, while such an increase could be downregulated by baicalin. Baicalin attenuates gentamicin-induced cochlear hair cells ototoxicity, and such inhibition may be mediated by the regulation of reactive oxygen species production, mitochondrial depolarization, and caspase-3 and PARP activation.

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Section: Discussionmentioning

confidence: 99%

Baicalin attenuates gentamicin‐induced cochlear hair cell ototoxicity

Xian-fen

2019

J of Applied Toxicology

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“…Injection of magnetically labeled AdSCs into the cochlea of kanamycin deafened rats revealed elevations of BDNF, the presence of significant number of MSCs in the cochlea, improved survival of SGNs, and improved hearing threshold levels denoting to their protective effects against loss of auditory function [85]. Intravenous transplantation of intact human UCSCs in a deaf Guinea pig model revealed an improvement in hearing thresholds via relocation and a rise in the number of SGNs [86].…”

Section: In Vivo Studies Of Inner Ear Hearing Lossmentioning

confidence: 94%

“…Injection of human olfactory stem cells (OSCs) into cochleae of mice, via lateral wall cochleostomy, with early onset progressive SNHL resulted in a reduction in inflammation, oxidative stress, cell apoptosis, a significant lower hearing threshold level, and amelioration of hearing loss [90]. The human MSCs, derived from nasal tissue, were evidenced to repair spiral ganglion loss in experimentally injured cochlear of neonatal rats via direct neuronal differentiation and secondary effects on endogenous cells [91] that can be tracked and verified, in a non-invasive manner, after cell transplantation by using MRI contrast agents [79,85,92].…”

Section: In Vivo Studies Of Inner Ear Hearing Lossmentioning

confidence: 99%

Achievements and Challenges in Transplantation of Mesenchymal Stem Cells in Otorhinolaryngology

Kaboodkhani

Mehrabani

Karimi‐Busheri

2021

JCM

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Otorhinolaryngology enrolls head and neck surgery in various tissues such as ear, nose, and throat (ENT) that govern different activities such as hearing, breathing, smelling, production of vocal sounds, the balance, deglutition, facial animation, air filtration and humidification, and articulation during speech, while absence of these functions can lead to high morbidity and even mortality. Conventional therapies for head and neck damaged tissues include grafts, transplants, and artificial materials, but grafts have limited availability and cause morbidity in the donor site. To improve these limitations, regenerative medicine, as a novel and rapidly growing field, has opened a new therapeutic window in otorhinolaryngology by using cell transplantation to target the healing and replacement of injured tissues. There is a high risk of rejection and tumor formation for transplantation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs); mesenchymal stem cells (MSCs) lack these drawbacks. They have easy expansion and antiapoptotic properties with a wide range of healing and aesthetic functions that make them a novel candidate in otorhinolaryngology for craniofacial defects and diseases and hold immense promise for bone tissue healing; even the tissue sources and types of MSCs, the method of cell introduction and their preparation quality can influence the final outcome in the injured tissue. In this review, we demonstrated the anti-inflammatory and immunomodulatory properties of MSCs, from different sources, to be safely used for cell-based therapies in otorhinolaryngology, while their achievements and challenges have been described too.

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“…It is believed that MSCs generally do not give rise to new neurons or hair cells, but exert their anti-inflammatory properties and neurotrophic support through paracrine signaling to protect a variety of damaged cells in the cochlea, e.g., neurons, hair cells, fibrocytes, and promote regeneration ( Yoo et al, 2015 ; Kanzaki et al, 2020 ). MSC labeled with superparamagnetic nanoparticles were developed to improve homing to the cochlea after systemic injection, using a magnetized cochlear implant and external magnet ( Le et al, 2017 ). Magnetically targeted MSCs entered the cochlea and preserved SGN population (80% survival at 4 weeks) and lowered the click ABR thresholds to 75 dB compared to 84 dB in control rats ( p < 0.05).…”

Section: Cell Therapy and Delivery Methodsmentioning

confidence: 99%

Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities

Liu

Yang

2022

Front. Neurosci.

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Most therapies for treating sensorineural hearing loss are challenged by the delivery across multiple tissue barriers to the hard-to-access anatomical location of the inner ear. In this review, we will provide a recent update on various pharmacotherapy, gene therapy, and cell therapy approaches used in clinical and preclinical studies for the treatment of sensorineural hearing loss and approaches taken to overcome the drug delivery barriers in the ear. Small-molecule drugs for pharmacotherapy can be delivered via systemic or local delivery, where the blood-labyrinth barrier hinders the former and tissue barriers including the tympanic membrane, the round window membrane, and/or the oval window hinder the latter. Meanwhile, gene and cell therapies often require targeted delivery to the cochlea, which is currently achieved via intra-cochlear or intra-labyrinthine injection. To improve the stability of the biomacromolecules during treatment, e.g., RNAs, DNAs, proteins, additional packing vehicles are often required. To address the diverse range of biological barriers involved in inner ear drug delivery, each class of therapy and the intended therapeutic cargoes will be discussed in this review, in the context of delivery routes commonly used, delivery vehicles if required (e.g., viral and non-viral nanocarriers), and other strategies to improve drug permeation and sustained release (e.g., hydrogel, nanocarriers, permeation enhancers, and microfluidic systems). Overall, this review aims to capture the important advancements and key steps in the development of inner ear therapies and delivery strategies over the past two decades for the treatment and prophylaxis of sensorineural hearing loss.

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Magnetic stem cell targeting to the inner ear

Cited by 14 publications

References 79 publications

Baicalin attenuates gentamicin‐induced cochlear hair cell ototoxicity

Baicalin attenuates gentamicin‐induced cochlear hair cell ototoxicity

Achievements and Challenges in Transplantation of Mesenchymal Stem Cells in Otorhinolaryngology

Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities

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