Table 1.
In vivo studies to restore auditory nerve function.
| Study | Site of donor cell delivery | Host animal Deafening procedure |
Verification of functional restoration and synaptogenesis | Donor cell* |
|---|---|---|---|---|
| Cell delivery into the cochlea | ||||
| Hu et al. (2004)79 | ScT (MLI) | Rat Pharmacol, local# |
No | Mouse DRGC |
| Hu et al. (2005)78 | ditto | Guinea pig Pharmacol, local |
No | Mouse ESC and DRGC |
| Hu et al. (2005)80 | ditto | Guinea pig Pharmacol, local |
No | Mouse NSC |
| Coleman et al. (2006)71 | ditto | Guinea pig Pharmacol, systemic** |
No | Mouse ESC |
| Matsuoka et al. (2007)86 | ditto | Gerbil Pharmacol, local |
No | Mouse MSC |
| Parker et al. (2007)87 | ditto | Mouse/guinea pig Sound exposure |
No | Mouse NSC |
| Altschuler et al. (2008)68 | ditto | Guinea pig Pharmacol, systemic |
No | Mouse ESC |
| Lang et al. (2008)85 | ditto | Gerbil Pharmacol, local |
No | Mouse ESC |
| Hu et al. (2009)81 | ditto | Guinea pig Pharmacol, systemic |
No | Mouse DRGC |
| Cho et al. (2011)70 | ditto | Guinea pig Pharmacol, local |
No | Human MSC |
| Pettingill et al. (2011)88 | ditto | Guinea pig Pharmacol, systemic |
No | Schwann cells |
| Warnecke et al. (2012)90 | ditto | Guinea pig Pharmacol, systemic |
No | BDNF-secreting cells |
| He et al. (2014)76 | ditto | Guinea pig Pharmacol, local |
No | Mouse NSC |
| Jang et al. (2015)84 | ditto | Guinea pig Pharmacol, local |
No | Human MSC |
| Fetoni et al. (2014)73 | ditto | Guinea pig Noise exposure |
No | Guinea pig ADSC |
| Gillespie et al. (2015)74 | ditto | Guinea pig Pharmacol, systemic |
No | BDNF-expressing fibroblast |
| Jang et al. (2016)83 | ditto | Guinea pig Pharmacol, local |
No | Human ADSC |
| Xu et al. (2016)92 | ditto | Rat Noise exposure |
No | olfactory epithelium NSC |
| Dai et al. (2016)72 | ditto | Rat Pharmacol, systemic |
No | Rat OEC |
| Wise et al. (2016)91 | ditto | Guinea pig Pharmacol, systemic |
No | Human ESC |
| Chen et al. (2017)69 | ditto | Mouse Pharmacol, systemic |
No | Mouse iPSC |
| Schendzielorz et al. (2017)89 | ditto | Guinea pig Pharmacol, local |
No | Guinea pig ADSC |
| Huang et al. (2019)82 | ditto | Gerbil Pharmacol, local |
No | Mouse NSC |
| Hildebrand et al. (2005)77 | ScM (MLI) | Guinea pig Pharmacol, systemic |
No | Mouse ESC |
| Hu et al. (2005)80 | ditto | Guinea pig Pharmacol, local |
No | Mouse ESC mouse DRGC |
| Lang et al. (2008)85 | ScM, RC (MLI) | Gerbil Pharmacol, local |
No | Mouse ESC |
| Ahn et al. (2008)67 | PSCC (MLI) | Mouse Pharmacol, systemic |
No | Mouse ESC |
| Zhang et al. (2013)65,66 | Cochlea wall (MLP) | Rat Pharmacol, local |
No | Mouse NSC |
| Hackelberg et al. (2017)75 | Scaffold in IAC (MLI) | Guinea pit Pharmacol, local |
No | Human ESC |
| Direct cell injection into auditory nerve (MLI) | ||||
| Tamura et al. (2004)101 | AuN | Mouse Pharmacol, local |
No | Mouse NSC |
| Naito et al. (2004)95 | ditto | Chinchilla Pharmacol, systemic |
No | Bone marrow cell |
| Hu et al. (2004)94 | ditto | Rat Transected AuN |
No | Mouse DRGC, ESC |
| Okano et al. (2005)97 | ditto | Guinea pig Pharmacol, systemic |
No | Mouse ESC |
| Regala et al. (2005)98 | ditto | Guinea pig, rat Pharmacol, systemic |
No | Mouse DRGC |
| Corrales et al. (2006)93 | ditto | Gerbil Pharmacol, local |
No | Mouse ESC |
| Matsuoka et al. (2007)86 | ditto | Gerbil Pharmacol, local |
No | Mouse MSC |
| Shi et al. (2007)100 | ditto | Gerbil Pharmacol, local |
No | Human ESC |
| Altschuler et al. (2008)68 | ditto | Guinea pig Pharmacol, systemic |
No | Mouse ESC |
| Reyes et al. (2008)99 | ditto | Guinea pig Pharmacol, systemic |
No | Mouse ESC |
| Ogita et al. (2010)96 | ditto | Guinea pig Pharmacol, local |
No | Guinea pig MSC-derived spheres |
| Chen et al. (2012)22 | ditto | Gerbil Pharmacol, local |
Yes | Human ESC |
| Direct cell injection into the auditory nerve (MLP) | ||||
| Sekiya et al. (2006)107 | AuN | Rat Compression of AuN | No | Mouse ESC |
| Sekiya et al. (2007)106 | ditto | ditto | No | Mouse auditory neuroblast |
| Palmgren et al. (2012)105 | ditto | Rat Pharmacol, local |
No | Mouse ESC |
| Jiao et al. (2014)104 | ditto | Rat Pharmacol, local |
No | Human neural precursors |
| Chen et al. (2019)103 | ditto | Mouse Pharmacol, local |
No | Human limbus-derived MSC |
| Cell transplantation onto the auditory nerve (MLP) | ||||
| Sekiya et al. (2015)2 | AuN |
Rat Compression of AuN |
Yes | Mouse auditory neuroblast |
| Systemic delivery (MLP) | ||||
| Revoltella et al. (2008)63 | i.v. | Mouse Pharmacol, systemic Noise |
No | Human cord blood stem cells |
| Choi et al. (2012)58 | i.v. | Rat Noise Pharmacol, local |
No | Human MSC |
| Choi et al. (2012)57 | i.v. | Guinea pig Pharmacol, local |
No | Human blood MSC |
| Yoo et al. (2015)64 | i.v. | Autoimmune hearing loss mouse | No | Human ADSC |
| Lang et al. (2016)60 | i.v. | Mouse Pharmacol, local |
No | Mouse and human blood cell |
| Kil et al. (2016)59 | i.v. | Guinea pig Pharmacol, local |
No | MSC from human placenta |
| Ma et al. (2016)62 | i.t. | Congenital deaf albino pig | No | Human umbilical cord MSC |
| Lee et al. (2018)61 | i.v. | Human cases | No | MSC |
| Abd El Raouf et al. (2019)56 | i.v. | Guinea pig Pharmacol, systemic |
No | Guinea pig Harderian gland stem cells |
ABR, auditory brainstem responses; ADSC, adipose tissue-derived stem cell; AuN, auditory nerve; BDNF, brain-derived neurotrophic factor; CPA, cerebellopontine angle; DPOAE, distortion product otoacoustic emissions; DRGC, dorsal root ganglion cell; ESC, embryonic stem cell; IAM, internal auditory meatus; iPSC, induced pluripotent stem cell; i.t., intrathecal injection; i.v., intravenous injection; MLI, membranous labyrinth injured; MLP, membranous labyrinth preserved; MSC, mesenchymal stem cell; NSC, neural stem cell; OEC, olfactory ensheathing cell; RC, Rosenthal’s canal; Ref, reference number; ScM, the scala media; ScT, the scala tympani; ScV, the scala vestibuli.
* “Donor cell” indicates the provenance of donor cell. Donor cells may have been preconditioned in vitro before transplantation. For example, application of neural induction for ESC.
# “Pharmacol, local” indicates that pharmacological agents were applied locally to the auditory system. For example, ouabain applied to the round window of the cochlea.
** “Pharmacol, systemic” indicates application intravenously. For example, ototoxic antibiotics such as kanamycin injected in the tail vein of the host.
Note: Studies using more than one cell delivery routes are repeatedly listed in Table 1. The references in the text and table are listed basically in chronological order.