Published online before print May 24, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.060948

Accepted for publication March 26, 2007.

Article

Mesenchymal Stem Cell Transplantation Accelerates Hearing Recovery through the Repair of Injured Cochlear Fibrocytes

Kazusaku Kamiya^*, Yoshiaki Fujinami^*, Noriyuki Hoya^*, Yasuhide Okamoto^*, Hiroko Kouike^*, Rie Komatsuzaki^*, Ritsuko Kusano^*, Susumu Nakagawa^*, Hiroko Satoh, Masato Fujii, and Tatsuo Matsunaga^*@

From the Laboratory of Auditory Disorders* and Division of Hearing and Balance Research, National Institute of Sensory Organs, and the Department of Plastic Surgery, National Tokyo Medical Center, Tokyo, Japan

^@ To whom correspondence should be addressed. E-mail: matsunagatatsuo{at}kankakuki.go.jp.

	Abstract

Cochlear fibrocytes play important roles in normal hearing as well as in several types of sensorineural hearing loss attributable to inner ear homeostasis disorders. Recently, we developed a novel rat model of acute sensorineural hearing loss attributable to fibrocyte dysfunction induced by a mitochondrial toxin. In this model, we demonstrate active regeneration of the cochlear fibrocytes after severe focal apoptosis without any changes in the organ of Corti. To rescue the residual hearing loss, we transplanted mesenchymal stem cells into the lateral semicircular canal; a number of these stem cells were then detected in the injured area in the lateral wall. Rats with transplanted mesenchymal stem cells in the lateral wall demonstrated a significantly higher hearing recovery ratio than controls. The mesenchymal stem cells in the lateral wall also showed connexin 26 and connexin 30 immunostaining reminiscent of gap junctions between neighboring cells. These results indicate that reorganization of the cochlear fibrocytes leads to hearing recovery after acute sensorineural hearing loss in this model and suggest that mesenchymal stem cell transplantation into the inner ear may be a promising therapy for patients with sensorineural hearing loss attributable to degeneration of cochlear fibrocytes.