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Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a guinea pig model.

Tan CQ, Gao X, Guo L, Huang H - Biomed Res Int (2014)

Bottom Line: Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05).Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4.Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China ; Department of Otolaryngology-Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.

ABSTRACT
Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

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Related in: MedlinePlus

(a, b) Vertical slices of cochlea in Group A (20 × 10); clumps of cells colored brown in scala tympani could be seen, indicating positive enzyme reactions. The lips of the osseous spiral lamina also showed positive staining (indicated by the arrow). (c) Vertical slice of cochlea from a guinea pig in Group B (10 × 10); clumps of cells were seen in scala tympani (indicated by the arrow). Neither the clumps of cells nor any other parts of the inner ear were stained brown. (d) Vertical slice of cochlea from a guinea pig in Group C; brown staining was not seen. Scattered blood cells in scala tympani were a result of the bleeding during the injection (indicated by the arrow).
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fig7: (a, b) Vertical slices of cochlea in Group A (20 × 10); clumps of cells colored brown in scala tympani could be seen, indicating positive enzyme reactions. The lips of the osseous spiral lamina also showed positive staining (indicated by the arrow). (c) Vertical slice of cochlea from a guinea pig in Group B (10 × 10); clumps of cells were seen in scala tympani (indicated by the arrow). Neither the clumps of cells nor any other parts of the inner ear were stained brown. (d) Vertical slice of cochlea from a guinea pig in Group C; brown staining was not seen. Scattered blood cells in scala tympani were a result of the bleeding during the injection (indicated by the arrow).

Mentions: After IHC, cell clumps in the scala tympani and the lips of the osseous spiral lamina of animals in Group A showed obvious brown color (Figures 7(a) and 7(b)), indicating that enzyme reactions were positive. The organ of Corti and spiral ganglion showed weak staining. In group B (Figure 7(c)), no evidence of positive enzyme reactions in cell clumps in the scala tympani or other parts of the inner ear was found. In Group C (Figure 7(d)), no evidence of positive enzyme reactions was found in the inner ear.


Exogenous IL-4-expressing bone marrow mesenchymal stem cells for the treatment of autoimmune sensorineural hearing loss in a guinea pig model.

Tan CQ, Gao X, Guo L, Huang H - Biomed Res Int (2014)

(a, b) Vertical slices of cochlea in Group A (20 × 10); clumps of cells colored brown in scala tympani could be seen, indicating positive enzyme reactions. The lips of the osseous spiral lamina also showed positive staining (indicated by the arrow). (c) Vertical slice of cochlea from a guinea pig in Group B (10 × 10); clumps of cells were seen in scala tympani (indicated by the arrow). Neither the clumps of cells nor any other parts of the inner ear were stained brown. (d) Vertical slice of cochlea from a guinea pig in Group C; brown staining was not seen. Scattered blood cells in scala tympani were a result of the bleeding during the injection (indicated by the arrow).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016942&req=5

fig7: (a, b) Vertical slices of cochlea in Group A (20 × 10); clumps of cells colored brown in scala tympani could be seen, indicating positive enzyme reactions. The lips of the osseous spiral lamina also showed positive staining (indicated by the arrow). (c) Vertical slice of cochlea from a guinea pig in Group B (10 × 10); clumps of cells were seen in scala tympani (indicated by the arrow). Neither the clumps of cells nor any other parts of the inner ear were stained brown. (d) Vertical slice of cochlea from a guinea pig in Group C; brown staining was not seen. Scattered blood cells in scala tympani were a result of the bleeding during the injection (indicated by the arrow).
Mentions: After IHC, cell clumps in the scala tympani and the lips of the osseous spiral lamina of animals in Group A showed obvious brown color (Figures 7(a) and 7(b)), indicating that enzyme reactions were positive. The organ of Corti and spiral ganglion showed weak staining. In group B (Figure 7(c)), no evidence of positive enzyme reactions in cell clumps in the scala tympani or other parts of the inner ear was found. In Group C (Figure 7(d)), no evidence of positive enzyme reactions was found in the inner ear.

Bottom Line: Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05).Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4.Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 5 Xinmofan Road, Nanjing, Jiangsu 210009, China ; Department of Otolaryngology-Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.

ABSTRACT
Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups (P < 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.

Show MeSH
Related in: MedlinePlus