Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss

Schendzielorz, Philipp; Vollmer, Maike; Rak, Kristen; Wiegner, Armin; Nada, Nashwa; Radeloff, Katrin; Hagen, Rudolf; Radeloff, Andreas

doi:10.1016/j.jcyt.2017.07.007

Cited by 4 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study further evaluates the application of autologous ASCs into the inner ear before insertion of a cochlear implant for protecting SGN survival in an animal model for sensory hearing loss. In animals treated with ASCs prior to insertion of the cochlear implant, the loss of SGNs was significantly reduced to a degree that is comparable to a prior study on ASC transplantation without cochlear implant insertion [17]. In addition, in ASC-transplanted deaf cochleae, the density of peripheral processes was significantly higher compared to cochleae in both the cochlear implant-only group and the untreated controls.…”

Section: Discussionsupporting

confidence: 74%

“…ASCs were isolated from adipose tissue of the neck of each individual animal as described before [17]. The isolation of ASCs was performed according to a modified protocol described by Zuk et al [18].…”

Section: Isolation Of Adipose-derived Stromal Cells Transplantation O...mentioning

confidence: 99%

“…After the final experiment, animals were euthanized, and the cochleae were processed as described earlier [17]. To determine the SGN survival, 5 mid modiolar sections were stained with Haematoxylin (Merck, Germany) and Eosin (Merk), and images were taken of the Rosenthal's canal using a transmitted light microscope (LaborLux-S Leica) and a color video camera (Sony 3 CCD; Sony).…”

Section: Analysis Of Neuron Survival and Neurite Densitymentioning

confidence: 99%

See 2 more Smart Citations

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation

Radeloff¹,

Nada

Mahallawi

et al. 2021

NeuroReport

Self Cite

View full text Add to dashboard Cite

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASCtransplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to longterm benefits in speech discrimination performance in cochlear implant subjects. NeuroReport 32: 776-782

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Isolation Of Adipose-derived Stromal Cells Transplantation O...mentioning

confidence: 99%

Section: Analysis Of Neuron Survival and Neurite Densitymentioning

confidence: 99%

See 1 more Smart Citation

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation

Radeloff¹,

Nada

Mahallawi

et al. 2021

NeuroReport

Self Cite

View full text Add to dashboard Cite

show abstract

“…According to Global Burden of Disease study 2019 (GBD2019), about 5% (1,456,662,173 people) of the world's population is suffering from hearing impairment [1], with a years lived with disability (YLDs) of 43.45 million, among which 7 million were attributable to occupational noise exposure [2]. Unlike the few progress in drug therapy, mesenchymal stem cell (MSC) transplantation was proved effective in multiple sensorineural hearing loss [3][4][5][6][7], but the mechanism behind remained unclear. As traditional acknowledgment, the effect of MSCs based on their ability of homing [8] and multi-differentiation to replace the injured cells.…”

Section: Introductionmentioning

confidence: 99%

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway

et al. 2023

View full text Add to dashboard Cite

Background Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet. Methods Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways. Results We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)—mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs. Conclusions These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.

show abstract

“…This does not seem to be the case, and none of the relevant studies have led to functional recovery ( Table 1 ). With the exception of two studies 65 , 66 , the membrane that seals intracochlear fluid-containing spaces (the membranous labyrinth = the scala tympani, scala vestibuli, the scala media, and posterior semicircular canal) was breached and/or trespassed (membranous labyrinth injured [MLI]) 67 – 92 ( Table 1 ). Importantly, invasion into the membranous labyrinth is clinically unacceptable because it leads to hearing loss 3 .…”

Section: Introductionmentioning

confidence: 99%

Cell Transplantation to Restore Lost Auditory Nerve Function is a Realistic Clinical Opportunity

Sekiya

Holley

2021

Cell Transplant

View full text Add to dashboard Cite

Hearing is one of our most important means of communication. Disabling hearing loss (DHL) is a long-standing, unmet problem in medicine, and in many elderly people, it leads to social isolation, depression, and even dementia. Traditionally, major efforts to cure DHL have focused on hair cells (HCs). However, the auditory nerve is also important because it transmits electrical signals generated by HCs to the brainstem. Its function is critical for the success of cochlear implants as well as for future therapies for HC regeneration. Over the past two decades, cell transplantation has emerged as a promising therapeutic option for restoring lost auditory nerve function, and two independent studies on animal models show that cell transplantation can lead to functional recovery. In this article, we consider the approaches most likely to achieve success in the clinic. We conclude that the structure and biochemical integrity of the auditory nerve is critical and that it is important to preserve the remaining neural scaffold, and in particular the glial scar, for the functional integration of donor cells. To exploit the natural, autologous cell scaffold and to minimize the deleterious effects of surgery, donor cells can be placed relatively easily on the surface of the nerve endoscopically. In this context, the selection of donor cells is a critical issue. Nevertheless, there is now a very realistic possibility for clinical application of cell transplantation for several different types of hearing loss.

show abstract

Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss

Cited by 4 publications

References 48 publications

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation

Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway

Cell Transplantation to Restore Lost Auditory Nerve Function is a Realistic Clinical Opportunity

Contact Info

Product

Resources

About