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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

BMSC morphology in culture. BMSCs (passage 3) observed under an inverted microscope (×100); uniform spindle-shaped BMSCs fused into a spiral shape.
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fig1: BMSC morphology in culture. BMSCs (passage 3) observed under an inverted microscope (×100); uniform spindle-shaped BMSCs fused into a spiral shape.

Mentions: Guinea pig BMSCs were separated using a previously described adherence method with modifications [16, 17] and were cultured in DMEM. The main difference from the traditional method is that we shortened the interval of changing cell medium in the early primary culture, 3 h for the first time and 8 h for the rest of times. This can greatly remove the contaminating cells-hematopoietic stem cells (HSCs). The digestive time by trypsin was shortened from 5~6 min to 2 min in order to avoid reducing the activity of MSCs. After 3 passages, BMSCs were obtained at high purity ready for lentiviral infection (shown in Figure 1).


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)

BMSC morphology in culture. BMSCs (passage 3) observed under an inverted microscope (×100); uniform spindle-shaped BMSCs fused into a spiral shape.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: BMSC morphology in culture. BMSCs (passage 3) observed under an inverted microscope (×100); uniform spindle-shaped BMSCs fused into a spiral shape.
Mentions: Guinea pig BMSCs were separated using a previously described adherence method with modifications [16, 17] and were cultured in DMEM. The main difference from the traditional method is that we shortened the interval of changing cell medium in the early primary culture, 3 h for the first time and 8 h for the rest of times. This can greatly remove the contaminating cells-hematopoietic stem cells (HSCs). The digestive time by trypsin was shortened from 5~6 min to 2 min in order to avoid reducing the activity of MSCs. After 3 passages, BMSCs were obtained at high purity ready for lentiviral infection (shown in Figure 1).

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