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

Research output: Contribution to journalArticle

Abstract

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
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue numberSUPPL. 1
Publication statusPublished - 13-11-2007

Fingerprint

Cochlea
Hematopoietic Stem Cells
Cell Death
Ischemia
Sudden Hearing Loss
Hearing Loss
Vertebrobasilar Insufficiency
Glial Cell Line-Derived Neurotrophic Factor
Vertebral Artery
Gerbillinae
Sensorineural Hearing Loss
Alopecia
Deafness
Outer Auditory Hair Cells
Inner Auditory Hair Cells
Stem Cells
Cervical Vertebrae
Organ of Corti
Hematopoietic Stem Cell Transplantation
Inner Ear

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Yoshida, Tadashi ; Hata, Ryuji ; Hakuba, Nobuhiro ; Cao, Fang ; Zhu, Pengxiang ; Sakanaka, Masahiro ; Gyo, Kiyofumi. / Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects. In: Journal of Cerebral Blood Flow and Metabolism. 2007 ; Vol. 27, No. SUPPL. 1.
@article{be9b8c4bc3fb400ea4c71c24d15e6830,
title = "Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects",
abstract = "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.",
author = "Tadashi Yoshida and Ryuji Hata and Nobuhiro Hakuba and Fang Cao and Pengxiang Zhu and Masahiro Sakanaka and Kiyofumi Gyo",
year = "2007",
month = "11",
day = "13",
language = "English",
volume = "27",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "SUPPL. 1",

}

Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects. / Yoshida, Tadashi; Hata, Ryuji; Hakuba, Nobuhiro; Cao, Fang; Zhu, Pengxiang; Sakanaka, Masahiro; Gyo, Kiyofumi.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 27, No. SUPPL. 1, 13.11.2007.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects

AU - Yoshida, Tadashi

AU - Hata, Ryuji

AU - Hakuba, Nobuhiro

AU - Cao, Fang

AU - Zhu, Pengxiang

AU - Sakanaka, Masahiro

AU - Gyo, Kiyofumi

PY - 2007/11/13

Y1 - 2007/11/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=36349029619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36349029619&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:36349029619

VL - 27

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - SUPPL. 1

ER -