Mol Ther. 2016 Sep 7. doi: 10.1038/mt.2016.174. [Epub ahead of print]

Contributions of mouse and human hematopoietic cells to remodeling of the adult auditory nerve after neuron loss.

Lang H¹, Nishimoto E¹, Xing Y¹, Brown LN¹, Noble KV¹, Barth JL², LaRue AC^1,3, Ando K⁴, Schulte BA¹.

Abstract

The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier. This procedure also resulted in the upregulation of genes associated with hematopoietic cell homing and differentiation, and provided an environment conducive to the tissue engraftment of circulating stem/progenitor cells into the AN. Experiments were performed using both a mouse-mouse bone marrow transplantation model and a severely immune-incompetent mouse model transplanted with human CD34⁺ cord blood cells. Quantitative immunohistochemical analysis of recipient mice demonstrated that ouabain injury promoted an increase in the number of both HSC-derived macrophages and HSC-derived non-macrophages in the AN. Although rare, a few HSC-derived cells in the injured AN exhibited glial-like qualities. These results suggest that human hematopoietic cells participate in remodeling of the AN after neuron cell body loss and that hematopoietic cells can be an important resource for promoting AN repair/regeneration in the adult inner ear.Molecular Therapy (2016); doi:10.1038/mt.2016.174.