Functional interaction between mesenchymal stem cells and spiral ligament fibrocytes

Sun, Guangwei; Fujisawa, Masato; Matsunaga, Tatsuo

doi:10.1002/jnr.23067

Cited by 13 publications

(13 citation statements)

References 68 publications

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“…D; Spicer and Schulte ; Sun et al. ). In the P12 cochlear structure, the branches were more abundant and form a ‘feathered’ structure that emanates from cell bodies defined by α7 GFP expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

The expression of nicotinic receptor alpha7 during cochlear development

2012

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Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern diminishes after E16.5 in a basal to apex progression, as Hensen's cells and cells of the spiral ligament acquire alpha7GFP expression. At birth and thereafter alpha7GFP also identifies a subset of spiral ganglion cells whose processes terminate on inner hair cells. Efferent fibers identified by peripherin or calcitonin gene-related protein do not coexpress alpha7GFP. In addition to cochlear structures, there is strong expression of alpha7GFP by cells of the central auditory pathways including the ventral posterior cochlear nucleus, lateral lemniscus, central inferior colliculus, and the medial geniculate nucleus. Our findings suggest that alpha7 expression by both neuronal and non-neuronal cells has the potential to impact multiple auditory functions through mechanisms that are not traditionally attributed to this receptor.

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Section: Resultsmentioning

confidence: 99%

The expression of nicotinic receptor alpha7 during cochlear development

2012

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“…Furthermore, those fractions were also positive for Pou3f4, which reflected their immature nature. Immature SLFs that residing in the mature SL might explain how SLFs repair or replace themselves in the early stage [26]. …”

Section: Discussionmentioning

confidence: 99%

Characterization of slow-cycling cells in the mouse cochlear lateral wall

Watanabe

Fujioka

et al. 2017

PLoS ONE

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Cochlear spiral ligament fibrocytes (SLFs) play essential roles in the physiology of hearing including ion recycling and the generation of endocochlear potential. In adult animals, SLFs can repopulate after damages, yet little is known about the characteristics of proliferating cells that support SLFs’ self-renewal. Here we report in detail about the characteristics of cycling cells in the spiral ligament (SL). Fifteen P6 mice and six noise-exposed P28 mice were injected with 5-bromo-2′-deoxyuridine (BrdU) for 7 days and we chased BrdU retaining cells for as long as 60 days. Immunohistochemistry revealed that the BrdU positive IB4 (an endotherial marker) negative cells expressed an early SLF marker Pou3f4 but negative for cleaved-Caspase 3. Marker studies revealed that type 3 SLFs displayed significantly higher percentage of BrdU+ cells compared to other subtypes. Notably, the cells retained BrdU until P72, demonstrating they were dividing slowly.In the noise-damaged mice, in contrast to the loss of the other types, the number of type 3 SLFs did not altered and the BrdU incorporating- phosphorylated Histone H3 positive type 3 cells were increased from day 1 to 14 after noise exposure. Furthermore, the cells repopulating type 1 area, where the cells diminished profoundly after damage, were positive for the type 3 SLF markers. Collectively, in the latral wall of the cochlea, type 3 SLFs have the stem cell capacity and may contribute to the endogenous regeneration of lateral wall spiral ligament. Manipulating type 3 cells may be employed for potential regenerative therapies.

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“…It is also widely known that an appropriate inflammatory response is essential for tissue recovery. Our previous studies showed that type II and IV fibrocytes in the spiral ligament divide after injury, and exogenous mesenchymal stem cell transplantation studies show that these cells promote fibrocyte proliferation both in vivo and in vitro [20]. CCL-type chemokines, such as CCL-2, are potent agents that recruit these cells [2], [4].…”

Section: Discussionmentioning

confidence: 99%

“…For tissue fixation, rats were deeply anesthetized with pentobarbital (as described above) and transcardially perfused with 4% paraformaldehyde. Paraffin sections were prepared as previously described [20]. Immunohistochemistry for Iba-1 and IL-6 was performed as previously described [6].…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Inhibition of Cochlear Mitochondrial Respiratory Chain Induces Secondary Inflammation in the Lateral Wall: A Potential Therapeutic Target for Sensorineural Hearing Loss

et al. 2014

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Cochlear lateral wall has recently been reported as a common site of inflammation, yet precise molecular mechanisms of the inflammatory responses remain elucidated. The present study examined the inflammatory responses in the lateral wall following acute mitochondrial dysfunction induced by a mitochondrial toxin, 3-nitropropionic acid (3-NP). Reverse-transcription (RT)-PCR revealed increases in the expression of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Immunohistochemistry showed an increase in the number of activated cochlear macrophages in the lateral wall, which were in close proximity to IL-6-expressing cells. A genome-wide DNA microarray analysis of the lateral wall revealed that 35% and 60% of the genes showing >2-fold upregulation at 1 d and 3 d post-3-NP administration, respectively, were inflammatory genes, including CC- and CXC-type chemokine genes. High expression of CCL-1, 2, and 3 at 1 d, and of CCL-1, 2, 3, 4, and 5, CCR-2 and 5, and CX3CR1 at 3 d post-3-NP administration, coupled with no change in the level of CX3CL1 expression suggested that macrophages and monocytes may be involved in the inflammatory response to 3-NP-mediated injury. Quantitative (q)RT-PCR showed a transient induction of IL-1β and IL-6 expression within 24 h of 3-NP-mediated injury, followed by sustained expression of the chemoattractants, CCL-2, 4 and 5, up until 7 d after injury. The expression of CCL-2 and IL-6 was higher in animals showing permanent hearing impairment than in those showing temporary hearing impairment, suggesting that these inflammatory responses may be detrimental to hearing recovery. The present findings suggest that acute mitochondrial dysfunction induces secondary inflammatory responses in the lateral wall of the cochlear and that the IL-6/CCL-2 inflammatory pathway is involved in monocyte activation. Therefore, these secondary inflammatory responses may be a potential post-insult therapeutic target for treatments aimed at preventing the damage caused by acute mitochondrial dysfunction in the cochlear lateral wall.

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Functional interaction between mesenchymal stem cells and spiral ligament fibrocytes

Cited by 13 publications

References 68 publications

The expression of nicotinic receptor alpha7 during cochlear development

The expression of nicotinic receptor alpha7 during cochlear development

Characterization of slow-cycling cells in the mouse cochlear lateral wall

Pharmacological Inhibition of Cochlear Mitochondrial Respiratory Chain Induces Secondary Inflammation in the Lateral Wall: A Potential Therapeutic Target for Sensorineural Hearing Loss

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