TY - JOUR
T1 - A xenograft model of vestibular schwannoma and hearing loss
AU - Dinh, Christine T.
AU - Bracho, Olena
AU - Mei, Christine
AU - Bas, Esperanza
AU - Fernandez-Valle, Cristina
AU - Telischi, Fred
AU - Liu, Xue Zhong
N1 - Funding Information:
Address correspondence and reprint requests to Christine T. Dinh, M.D., Department of Otolaryngology, University of Miami Miller School of Medicine, 1120 NW 14th Street, Suite 579, Miami, FL 33136; E-mail: ctdinh@med.miami.edu Sources of support that require acknowledgment: The cell-line utilized in this study was created in part through funding by the NIDCD 1R01DC010189-06 research grant to Dr. Cristina Fernandez-Valle Disclosure of funding received for this work from an organization: N/A The authors disclose no conflicts of interest.
Publisher Copyright:
© 2018, Otology & Neurotology, Inc.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Hypothesis: Microsurgical implantation of mouse merlin-deficient Schwann cells (MD-SC) into the cerebellopontine angle of immunodeficient rats will initiate tumor formation, hearing loss, and vestibular dysfunction. Background: The progress in identifying effective drug therapies for treatment of Neurofibromatosis type II (NF2) is limited by the availability of animal models of VS that develop hearing loss and imbalance. Methods: A microsurgical technique for implanting MD-SCs onto the cochleovestibular nerve of rats was developed. Ten Rowett Nude rats were implanted with either ∼10 5 MD-SCs expressing luciferase (N = 5) or vehicle (N = 5). Rats received bioluminescence imaging, auditory brainstem response testing, and were observed for head tilt every 2 weeks after surgery, for a total of 6 weeks. Tumors were harvested and processed with hematoxylin & eosin staining and immunohistochemistry was performed for S100. Results: Rats implanted with MD-SCs developed significantly higher tumor bioluminescence measurements and hearing threshold shifts at multiple frequencies by the 4th and 6th weeks post-implantation, compared with control rats. Rats implanted with MD-SCs also developed gross tumor. The tumor volume was significantly greater than nerve volumes obtained from rats in the control group. All rats with tumors developed a head tilt, while control rats had no signs of vestibular dysfunction. Tumors demonstrated histological features of schwannoma and express S100. Conclusion: Using this microsurgical technique, this xenograft rat model of VS develops tumors involving the cochleovestibular nerve, shifts in hearing thresholds, and vestibular dysfunction. This animal model can be used to investigate tumor-mediated hearing loss and perform preclinical drug studies for NF2.
AB - Hypothesis: Microsurgical implantation of mouse merlin-deficient Schwann cells (MD-SC) into the cerebellopontine angle of immunodeficient rats will initiate tumor formation, hearing loss, and vestibular dysfunction. Background: The progress in identifying effective drug therapies for treatment of Neurofibromatosis type II (NF2) is limited by the availability of animal models of VS that develop hearing loss and imbalance. Methods: A microsurgical technique for implanting MD-SCs onto the cochleovestibular nerve of rats was developed. Ten Rowett Nude rats were implanted with either ∼10 5 MD-SCs expressing luciferase (N = 5) or vehicle (N = 5). Rats received bioluminescence imaging, auditory brainstem response testing, and were observed for head tilt every 2 weeks after surgery, for a total of 6 weeks. Tumors were harvested and processed with hematoxylin & eosin staining and immunohistochemistry was performed for S100. Results: Rats implanted with MD-SCs developed significantly higher tumor bioluminescence measurements and hearing threshold shifts at multiple frequencies by the 4th and 6th weeks post-implantation, compared with control rats. Rats implanted with MD-SCs also developed gross tumor. The tumor volume was significantly greater than nerve volumes obtained from rats in the control group. All rats with tumors developed a head tilt, while control rats had no signs of vestibular dysfunction. Tumors demonstrated histological features of schwannoma and express S100. Conclusion: Using this microsurgical technique, this xenograft rat model of VS develops tumors involving the cochleovestibular nerve, shifts in hearing thresholds, and vestibular dysfunction. This animal model can be used to investigate tumor-mediated hearing loss and perform preclinical drug studies for NF2.
KW - Acoustic neuroma
KW - Auditory brainstem response
KW - Bioluminescence
KW - Hearing
KW - NF2
KW - Neurofibromatosis type II
KW - Tumor
KW - Vestibular schwannoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85048146554&partnerID=8YFLogxK
U2 - 10.1097/MAO.0000000000001766
DO - 10.1097/MAO.0000000000001766
M3 - Article
C2 - 29557843
AN - SCOPUS:85048146554
VL - 39
SP - e362-e369
JO - American Journal of Otology
JF - American Journal of Otology
SN - 1531-7129
IS - 5
ER -