Vascular regeneration in adult mouse cochlea stimulated by VEGF-A 165 and driven by NG2-derived cells ex vivo

Xiaohan Wang, Jinhui Zhang, Guangshuai Li, Na Sai, Jiang Han, Zhiqiang Hou, Allan Kachelmeier, Xiao Shi

Research output: Contribution to journalArticle

Abstract

Can damaged or degenerated vessels be regenerated in the ear? The question is clinically important, as disruption of cochlear blood flow is seen in a wide variety of hearing disorders, including in loud sound-induced hearing loss (endothelial injury), ageing-related hearing loss (lost vascular density), and genetic hearing loss (e.g., Norrie disease: strial avascularization). Progression in cochlear blood flow (CBF) pathology can parallel progression in hair cell and hearing loss. However, neither new vessel growth in the ear, nor the role of angiogenesis in hearing, have been investigated. In this study, we used an established ex vivo tissue explant model in conjunction with a matrigel matrix model to demonstrate for the first time that new vessels can be generated by activating a vascular endothelial growth factor (VEGF-A) signal. Most intriguingly, we found that the pattern of the newly formed vessels resembles the natural ‘mesh pattern’ of in situ strial vessels, with both lumen and expression of tight junctions. Sphigosine-1-phosphate (S1P) in synergy with VEGF-A control new vessel size and growth. Using transgenic neural/glial antigen 2 (NG2) fluorescent reporter mice, we have furthermore discovered that the progenitors of “de novo” strial vessels are NG2-derived cells. Taken together, our data demonstrates that damaged strial microvessels can be regenerated by reprogramming NG2-derived angiogenic cells. Restoration of the functional vasculature may be critical for recovery of vascular dysfunction related hearing loss.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalHearing Research
Volume377
DOIs
StatePublished - Jun 1 2019

Fingerprint

Cochlea
Hearing Loss
Neuroglia
Blood Vessels
Regeneration
Antigens
Vascular Endothelial Growth Factor A
Ear
Hearing Disorders
Tight Junctions
Alopecia
Growth
Microvessels
Hearing
Phosphates
human VEGFA protein
Pathology
Wounds and Injuries

Keywords

  • Angiogenesis
  • Mouse
  • Stria vascularis
  • VEGF-A

ASJC Scopus subject areas

  • Sensory Systems

Cite this

Vascular regeneration in adult mouse cochlea stimulated by VEGF-A 165 and driven by NG2-derived cells ex vivo . / Wang, Xiaohan; Zhang, Jinhui; Li, Guangshuai; Sai, Na; Han, Jiang; Hou, Zhiqiang; Kachelmeier, Allan; Shi, Xiao.

In: Hearing Research, Vol. 377, 01.06.2019, p. 179-188.

Research output: Contribution to journalArticle

Wang, Xiaohan ; Zhang, Jinhui ; Li, Guangshuai ; Sai, Na ; Han, Jiang ; Hou, Zhiqiang ; Kachelmeier, Allan ; Shi, Xiao. / Vascular regeneration in adult mouse cochlea stimulated by VEGF-A 165 and driven by NG2-derived cells ex vivo In: Hearing Research. 2019 ; Vol. 377. pp. 179-188.
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