Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects

Tadashi Yoshida, Ryuji Hata, Nobuhiro Hakuba, Fang Cao, Pengxiang Zhu, Masahiro Sakanaka, Kiyofumi Gyo

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Background and aims: Idiopathic sudden hearing loss (ISHL) is usually unilateral and can be anything within a range of a slight impairment of hearing to virtual deafness. One of the most common etiologies for ISHL is circulatory disturbance (most often vertebrobasilar ischemia). Vertebrobasilar ischemia (VBI) causes deafness because most of the auditory system including the inner ears is supplied from the vertebrobasilar system. ISHL of vascular cause is important for neurologists to recognize, because it sometimes appears as a warning sign of impending vertebrobasilar ischemic stroke. Previously, we produced cochlear ischemia by occluding both vertebral arteries in gerbils and established an animal model of ISHL [1]. We also showed progressive sensory hair cell loss after cochlear ischemia [1]. Sensory hair cell loss results in the sensorineural hearing loss (SNHL) and the most common type of hearing loss in adults is SNHL. Recent advances in stem cell biology have gained interest in the hope that stem cell therapy will come closer to regenerating sensory hair cells. Transplantation of hematopoietic stem cells (HSC) is regarded to be a potential approach for promoting repair of damaged organs. Here, we investigated the influence of hematopoietic stem cells on progressive hair cell degeneration after transient cochlear ischemia in gerbils. Methods & Results: Transient cochlear ischemia was produced by extracranial occlusion of the bilateral vertebral arteries just before their entry into the transverse foramen of the cervical vertebra [2]. Intrascalar injection of HSC ameliorated hearing impairment (** indicates p< 0.01, n=6 in each group)(Fig. A) and prevented ischemia-induced inner hair cell (IHC) degeneration while there were no apparent outer hair cell (OHC) degeneration after ischemia (** indicates p< 0.01, n=6 in each group)(Fig. B). We also showed that the protein level of glial cell line-derived neurotrophic factor (GDNF) in the organ of Corti was upregulated after cochlear ischemia and that treatment with HSC augmented this ischemia-induced upregulation of GDNF. A tracking study revealed that HSC injected into the cochlea were retained in the perilymphatic space of the cochlea, although they neither transdifferentiated into cochlear cell types nor fused with the injured hair cells after ischemia. Conclusions: Our results suggest that HSC may have therapeutic potential possibly through paracrine effects. Thus, we propose HSC as a potential new therapeutic strategy for hearing loss.

Original languageEnglish
Pages (from-to)BP27-07H
JournalJournal of Cerebral Blood Flow and Metabolism
Issue numberSUPPL. 1
Publication statusPublished - 13-11-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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