Xenografted fetal dorsal root ganglion, embryonic stem cell and adult neural stem cell survival following implantation into the adult vestibulocochlear nerve

Abstract

Sensorineural hearing loss is a disabling condition. In the post-embryonic and adult mammalian inner ear, the regeneration of auditory hair cells, spiral ganglion neurons or their axons does not occur naturally. This decrease in excitable neurons limits the success of auditory rehabilitation. Allografts and xenografts have shown promise in the treatment of a variety of neurological diseases. Fetal dorsal root ganglion (DRG) neurons can extend functional connections in the rat spinal cord. Embryonic stem cells (ES cells) and adult neural stem cells (ANSC) have the potential to differentiate into neurons. We have implanted embryonic days (E) 13–16 fetal mouse DRGs from transgenic mouse lines that express Enhanced Green Fluorescent Protein (EGFP) or lacZ reporter genes, EGFP-expressing ES cells or lacZ-expressing ANSC into the injured vestibulocochlear nerve of adult rats and guinea pigs. Survival of the implants was assessed 2 to 4 weeks postoperatively. For further evaluation of the differentiation of the implanted ES-cells, we double labeled with the mouse-specific neuronal antibody Thy 1.2. The rats implanted with EGFP- or lacZ-expressing DRGs showed labeled DRGs after sacrifice. In addition, EGFP-positive nerve fibers were seen growing within the proximal nerve. The results from the EGFP ES cells and lacZ ANSC revealed reporter-expressing cells at the site of injection in the vestibulocochlear nerve of the host rats and guinea pigs but also within the brain stem. Thy 1.2 profiles were seen among the EGFP ES cells within the 8th cranial nerve. The findings of this study indicate that the vestibulocochlear nerve of adult rats and guinea pigs will support xenotransplants of embryonic DRG, ES cells and ANSC. This may have future clinical applicability in recreating a neuronal conduit following neuronal injury between the inner ear and the central nervous system (CNS).