Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model

Cho, Yong-Bum; Cho, Hyong‐Ho; Jang, Sujeong; Jeong, Han-Seong; Park, Jong-Seong

doi:10.3346/jkms.2011.26.4.492

Cited by 36 publications

(36 citation statements)

References 32 publications

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“…We found a nearly complete loss of SGNs in basal and middle turns ( Figure 5) as well as a profound shift in ABR threshold. Similar methods have recently been reported (Cho et al, 2011), but no normative data were provided on SGN loss by cochlear turn and, in contrast to our results, those authors reported no impact on sensory hair cells. We will establish a careful and systematic database of ouabain effects in the guinea pig ear that will be of broad use to other investigators exploring regenerative studies in the ouabain-treated guinea pig.…”

Section: Objective 1: Evaluate the Combination Of Genetic And Neurotrcontrasting

confidence: 54%

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

Duncan¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe chief aim of our study is restoration of hearing by regeneration of peripheral auditory neurons. The study takes a systematic approach in three objectives aiming to push human stem cells toward an auditory neural fate, embed the cells on a functionalized scaffold, and implant the device in a deafened animal model. In the first year of the project grant, we have addressed three key tasks: (1) derivation of sensory neurons from human pluripotent stem cells (hPSCs), (2) development of implantable nanofibrous substrates, and (3) optimization of the deafness model. In contrast to prior experiments in mouse embryonic stem cells, generation of sensory neurons simply by overexpression of neurogenin-1 in human embryonic stem cells was inefficient. As a result, we have established a small molecule programming strategy for producing sensory glutamatergic neurons that express otic transcriptional programs. These methods will be combined with neurogenin-1 overexpression to optimize derivation of auditory-like neurons. In addition, we developed novel methods for coiling a nanofiber scaffold to maintain the auditory nerve topology and establishing ouabain as an effective chemical tool for destroying endogenous auditory neurons in guinea pigs.

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Section: Objective 1: Evaluate the Combination Of Genetic And Neurotrcontrasting

confidence: 54%

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

Duncan¹

2013

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“…Cho et al delivered mesenchymal stem cells to hearing-impaired guinea pigs via the round window. They reported an increase in the spiral ganglion cells and improvement in the hearing status in ABRs (17).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the IPSCs that we used in our experiments were produced without the use of the c-myc oncogene, which might contribute to having more stable cells without teratoma formation (9). (17). Therefore, use of homograft or xenograft stem cells does not seem to affect the experiment, at least not in murine models.…”

Section: Could There Be a Difference Between Using Ipscs Or Other Typmentioning

confidence: 99%

“…Some authors advocate that an acute injury environment in cochleae induces pluripotent stem cells to migrate to the injury area and differentiate into hair cells (6,21). Others utilized certain procedures for inducing stem cells to differentiate into neural cell lineages (2,14,17,18). Further experiments are needed to provide better evidence on this subject.…”

Section: What Would Be the Further Directions For Future Studies?mentioning

confidence: 99%

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Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage*

et al. 2016

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Background/aim: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated.Materials and methods: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry.Results: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10-90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. Conclusion:Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

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“…Deafness animal models have been used to transplant MSCs differentiated into sensory neuronlike cells 27,33 . Indeed a useful approach for inner ear supplementation with stem cells can be hMSCs systemic application 34 .…”

Section: Hearing Recovery After Transplantation Of Mscsmentioning

confidence: 99%

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration

Mahmoudian-Sani

Mehri-Ghahfarrokhi

Hashemzadeh‐Chaleshtori

et al. 2017

The International Tinnitus Journal

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In this review, we compared the potential of mesenchymal stem cells derived from bone marrow, adipose tissue and umbilical cord as suitable sources for regeneration of inner ear hair cells and auditory neurons. Our intensive literature search indicates that stem cells in some of adult mammalian tissues, such as bone marrow, can generate new cells under physiological and pathological conditions. Among various types of stem cells, bone marrow-derived mesenchymal stem cells are one of the most promising candidates for cell replacement therapy. Mesenchymal stem cells have been reported to invade the damaged area, contribute to the structural reorganization of the damaged cochlea and improve incomplete hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells would be more beneficial than other mesenchymal stem cells.

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Transplantation of Neural Differentiated Human Mesenchymal Stem Cells into the Cochlea of an Auditory-neuropathy Guinea Pig Model

Cited by 36 publications

References 32 publications

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage*

Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue, and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration

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