Survival of Partially Differentiated Mouse Embryonic Stem Cells in the Scala Media of the Guinea Pig Cochlea

Abstract

The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

Transplantation of Mouse Embryonic Stem Cells into the Cochlea of an Auditory-Neuropathy Animal Model: Effects of Timing after Injury

“…Although we did identify a small number of ESCs in the scala media 2 weeks after transplantation, most of these cells were dead or dying based on morphological evidence of apoptosis. Another recent study has reported that partially differentiated mouse ESCs can survive in the endolymphatic space after transplantation into scala media of the guinea pig (Hildebrand et al 2006). A likely explanation for the ability of any cells to survive in the scala media is disruption of the normal tight-junction barrier between endolymph and perilymph by injection trauma.…”

“…Potential cell sources for inner ear transplantation include fetal dorsal root ganglion cells (Hu et al 2004;Regala et al 2005), neural progenitor cells (Ito et al 2001;Corrales et al 2006;), stem or progenitor cells isolated from inner ear (Li et al 2003a;Doetzlhofer et al 2004;Rask-Andersen et al 2005;Zhai et al 2005), immortalized auditory neuroblast cells (Nicholl et al 2005;Liu et al 2006a, b), ESCs and their derived neuronal cells (Li et al 2003b;Hu et al 2004Hu et al , 2005Hildebrand et al 2006;Okano et al 2005;Regala et al 2005;Coleman et al 2006;Sakamoto et al 2004;Sekiya et al 2006;Corrales et al 2006), and marrow stromal cells treated with sonic hedgehog and retinoic acid (Kondo et al 2005). ESCs derived from the inner cell mass of the blastocyst are capable of undergoing an unlimited number of divisions and differentiating into cell types of all three germ layers.…”

Genetic and pharmacological intervention for treatment/prevention of hearing loss

“…They have also shown that neural progenitors derived from mouse embryonic stem cells can integrate into a damaged cochlear nerve and send out neural processes toward the cochlea (Corrales et al, 2006). Several other groups have explored the use of mouse embryonic stem cells, bone marrow cells, or neural stem cells for repopulation of the cochlear nerve, organ of Corti, and lateral cochlear wall (Hildebrand et al, 2005;Lang et al, 2006;Matsuoka, Kondo, Miyamoto, & Hashino, 2006;Matsuoka, Kondo, Miyamoto, & Hashino, 2007).…”

Neurogene Stammzelltransplantation in die Kochlea

“…Die transplantierten Zellen konnten sogar noch nach mehreren Wochen im Innenohr nachgewiesen werden [6]. Kürzlich ist berichtet worden, dass die Zellen sich 9 Wochen nach Transplantation in der Scala media nachweisen ließen, allerdings ist es zu keiner Integration ins Corti-Organ gekommen, deshalb konnte auch keine Hörver-besserung im transplantierten Ohr im Vergleich zur unbehandelten Gegenseite nachgewiesen werden [4]. Obwohl wir in dieser Arbeit keine Daten über eine Integration der Vorläuferzellen ins Corti-Organ der Mäuse haben, halten wir dies eher für unwahrscheinlich.…”