Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage

Study of mouse induced pluripotent stem cell transplantation intoWistar albino rat cochleae after hair cell damage

Background/aim: As the regeneration capacity of hair cells is limited, inner ear stem cell therapies hold promise. Effects of mouse induced pluripotent stem cells (IPSCs) on Wistar albino rats (WARs) with hearing impairment were investigated. Materials and methods: Thirty-five adult WARs with normal hearing were divided into 4 groups. Excluding the study group (n = 15), the other three groups served as control groups for ototoxicity and IPSC injection models. IPSC injections were performed via cochleostomy after a retroauricular approach. Auditory functions were evaluated with auditory brainstem responses (ABRs) before and after the injections. After a final hearing assessment the WARs were sacrificed and cochleae were extracted to see the biologic behavior of IPSCs in the inner ear by light microscopy and immunohistochemistry. Results: There were no significant differences in the click-ABR thresholds in the study group after IPSC transplantation. The mean hearing threshold in the study group after ototoxic agent injection was 53.2 dB (10 90 dB). There was no significant difference between groups (P > 0.05) and no differentiated stem cells were observed immunohistochemically. Conclusion: Transplanted IPSCs did not show a therapeutic effect in this trial. We discuss potential pitfalls and factors affecting the therapeutic effect.

___

  • 1. Mills JH, Weber PC. Anatomy and physiology of hearing. In: Bailey BJ, Johnson JT, editors. Head & Neck Surgery: Otolaryngology. Philadelphia, PA, USA: LWW; 2006. pp. 1883- 1904.
  • 2. Li H, Corrales CE, Edge A, Heller S. Stem cells as therapy for hearing loss. Trends Mol Med 2004; 10: 309-315.
  • 3. Longworth-Mills E, Koehler KR, Hashino E. Generating inner ear organoids from mouse embryonic stem cells. Methods Mol Biol 2015; 1341: 391-406.
  • 4. Kamiya K. Inner ear cell therapy targeting hereditary deafness by activation of  stem cell  homing factors.  Front Pharmacol 2015; 6: 2.
  • 5. Corrales CE, Pan L, Li H, Liberman MC, Heller S, Edge AS. Engraftment and differentiation of embryonic stem cellderived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti. J Neurobiol 2006; 66: 1489-1500.
  • 6. Zhao LD, Li L, Wu N, Li DK, Ren LL, Guo WW, Sun LE, Liu HZ, Chen ZT, Xing GQ et al. Migration and differentiation of mouse embryonic stem cells transplanted into mature cochlea of rats with aminoglycoside-induced hearing loss. Acta Otolaryngol 2013; 133: 136-143.
  • 7. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 663-676.
  • 8. Nishimura K, Nakagawa T, Ono K, Ogita H, Sakamoto T, Yamamoto N, Okita K, Yamanaka S, Ito J. Transplantation of mouse induced pluripotent stem cells into the cochlea. Neuroreport 2009; 20: 1250-1254.
  • 9. Habib O, Habib G, Choi HW, Hong KS, Tae Do J, Moon SH, Chung HM. An improved method for the derivation of high quality iPSCs in the absence of c-Myc. Exp Cell Res 2013; 319: 3190-3200.
  • 10. Jero J, Tseng CJ, Mhatre AN, Lalwani AK. A surgical approach appropriate for targeted cochlear gene therapy in the mouse. Hearing Res 2001; 151: 106-114.
  • 11. Naito Y, Nakamura T, Nakagawa T, Iguchi F, Endo T, Fujino K, Kim TS, Hiratsuka Y, Tamura T, Kanemaru S et al. Transplantation of bone marrow stromal cells into the cochlea of chinchillas. Neuroreport 2004; 15: 1-4.
  • 12. Lu W, Xu J, Shepherd RK. Cochlear implantation in rats: a new surgical approach. Hearing Res 2005; 205: 115-122.
  • 13. Schlauch R, Nelson P. Pure tone evaluation. In: Burkard R, Hood L, Medwetzky L, Katz J, editors. Handbook of Clinical Audiology. 6th ed. Baltimore, MA, USA: Lippincott Williams & Williams; 2009. pp. 39-45.
  • 14. Ibekwe TS, Ramma L, Chindo BA. Potential roles of stem cells in the management of sensorineural hearing loss. J Laryngol Otol 2012; 126: 653-657.
  • 15. Sharif S, Nakagawa T, Ohno T, Matsumoto M, Kita T, Riazuddin S, Ito J. The potential use of bone marrow stromal cells for cochlear cell therapy. Neuroreport 2007; 18: 351-354.
  • 16. Hakuba N, Hata R, Morizane I, Feng G, Shimizu Y, Fujita K, Yoshida T, Sakanaka M, Gyo K. Neural stem cells suppress the hearing threshold shift caused by cochlear ischemia. Neuroreport 2005; 16: 1545-1549.
  • 17. Cho YB, Cho HH, Jang S, Jeong HS, Park JS. Transplantation of neural differentiated human mesenchymal stem cells into the cochlea of an auditory-neuropathy guinea pig model. J Korean Med Sci 2011; 26: 492-498.
  • 18. Okano T, Nakagawa T, Endo T, Kim TS, Kita T, Tamura T, Matsumoto M, Ohno T, Sakamoto T, Iguchi F et al. Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus. Neuroreport 2005; 16: 1919-1922.
  • 19. Oshima K, Shin K, Diensthuber M, Peng AW, Ricci AJ, Heller S. Mechanosensitive hair cell-like cells from embryonic and induced pluripotent stem cells. Cell 2010; 141: 704-716.
  • 20. Nishimura K, Nakagawa T, Sakamoto T, Ito J. Fates of murine pluripotent stem cell-derived neural progenitors following transplantation into mouse cochleae. Cell Transplant 2012; 21: 763-771.
  • 21. Hu Z, Wei D, Johansson CB, Holmstrom N, Duan M, Frisen J, Ulfendahl M. Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear. Exp Cell Res 2005; 302: 40-47.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: 6
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Health-related quality of life of pediatric renal transplant recipientsand their parents: the role of associated factors and clinical counseling

Necla BUYAN, Bülent ÇELİK, Bahar BÜYÜKKARAGÖZ, Nahide DOĞRUCAN

İrandokht Shenavar MASOOLEH, Asghar HAJIABBASI, Habib ZAYENI, Atefeh GHANBARI, Violet Zaker ESTEGHAMATI, Banafsheh Ghavidel PARSA, Amir HASSANKHANI

Determination of reference range with the indirect method of the 25-hydroxyvitaminD3 test in the Balıkesir region, Turkey

Medine ALPDEMİR, Mehmet Fatih ALPDEMİR

Hatice Gamze DEMİRDAĞ, Hamdi ÖZCAN, Şule GÜRSOY, Gülçin Beker AKBULUT

Chronic liver diseases and iron: a concise review with emphasis on hypotransferrinemia and hypohepcidinemia

Naciye Şemnur BÜYÜKAŞIK, Yahya BÜYÜKAŞIK

An assessment of adherence to asthma medication guidelines: findingsfrom a tertiary care center in the state of Penang, Malaysia

Raja Ahsan AFTAB, Amer Hayat KHAN, Syed Azhar SYED SULAIMAN, Irfhan ALI, Azmi HASSALI, Fahad SALEEM

Effect of resveratrol on resistin and apelin gene expressions in adipose tissue of diabetic rats

Jamshid KARIMI, Massoud SAIDIJAM, Sadegh ZAREI, Reza YADEGARAZARI, Azam REZAEI FARIMANI, Soulmaz-Sadat HOSSEINI-ZIJOUD, Mohammad Taghi GOODARZI

Xifeng WANG, Lianshuang ZHANG, Wei ZHAO, Tongshen LIU

Saima JABEEN, Sobia KANWAL, Mazhar QAYYUM, Umair FARRUKH, Shahzad Abdul HAMEED

The protective effects of hydrogen on HO-1 expression in the brainafter focal cerebral ischemia reperfusion in rats

Xifeng WANG, Lianshuang ZHANG, Tongshen LIU, Wei ZHAO