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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

Fluorescence microscopic assessment of inner ear tissue following immunization of experimental animals. (a) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group A (indicated by the arrow) (ST: scala tympani). (b) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group B. Fluorescence could also be detected in stria vascularis and vestibular membrane (indicated by the arrows). (c) Absence of fluorescent cells in scala tympani of a guinea pig from Group C, 1 week after injection with PBS. ST: scala tympani.
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fig6: Fluorescence microscopic assessment of inner ear tissue following immunization of experimental animals. (a) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group A (indicated by the arrow) (ST: scala tympani). (b) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group B. Fluorescence could also be detected in stria vascularis and vestibular membrane (indicated by the arrows). (c) Absence of fluorescent cells in scala tympani of a guinea pig from Group C, 1 week after injection with PBS. ST: scala tympani.

Mentions: In Groups A (Figure 6(a)) and B (Figure 6(b)), intense fluorescence from clumps of cells was observed in the scala tympani and scala vestibule after BMSC transplantation. Fluorescence was also observed in the stria vascularis, the lips of the osseous spiral lamina, and the organ of Corti, as well as under the vestibular membrane. No obvious fluorescence was detected in samples from Group C (Figure 6(c)).


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)

Fluorescence microscopic assessment of inner ear tissue following immunization of experimental animals. (a) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group A (indicated by the arrow) (ST: scala tympani). (b) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group B. Fluorescence could also be detected in stria vascularis and vestibular membrane (indicated by the arrows). (c) Absence of fluorescent cells in scala tympani of a guinea pig from Group C, 1 week after injection with PBS. ST: scala tympani.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Fluorescence microscopic assessment of inner ear tissue following immunization of experimental animals. (a) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group A (indicated by the arrow) (ST: scala tympani). (b) One week after transplantation of BMSCs, cell clumps emitting intense fluorescence were observed in the scala tympani of a guinea pig in Group B. Fluorescence could also be detected in stria vascularis and vestibular membrane (indicated by the arrows). (c) Absence of fluorescent cells in scala tympani of a guinea pig from Group C, 1 week after injection with PBS. ST: scala tympani.
Mentions: In Groups A (Figure 6(a)) and B (Figure 6(b)), intense fluorescence from clumps of cells was observed in the scala tympani and scala vestibule after BMSC transplantation. Fluorescence was also observed in the stria vascularis, the lips of the osseous spiral lamina, and the organ of Corti, as well as under the vestibular membrane. No obvious fluorescence was detected in samples from Group C (Figure 6(c)).

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