Adenoviral Mediated Gene Delivery to Human Umbilical Cord Mesenchymal Stromal Cells for Inner Ear Hair Cell Differentiation

Abstract

Hearing is one of our main sensory systems and having a hearing disorder, although not life threatening, can have a disturbing impact in an individual's quality of life. Approximately 49 million Americans suffer from some form of hearing loss. Sensory neural hearing loss (SNHL) is the most common form, which results from degeneration of inner ear sensory hair cells and auditory neurons in the cochlea. In recent years, there has been an increasing interest in gene delivery to mesenchymal stem cells. Gene delivery approaches to stem cells can provide an opportunity to engineer a variety of specialized cell types. The objective of this thesis was to evaluate the potential of human umbilical cord mesenchymal stromal cells (hUCMSCs) as a possible source for regenerating inner ear hair cells. This thesis was successful in developing an adenoviral mediated gene delivery approach to deliver the Math1 gene to hUCMSCs. The expression of Math1 induced the differentiation of hUCMSCs into cells that resembled inner ear hair cells morphologically and immunocytochemically, evidenced by the expression of hair cell-specific and glial cell markers. The results obtained in this thesis demonstrated for the first time that hUCMSCs can differentiate into hair cell-like cells, thus introducing a potential tissue engineering and cell transplantation approach for the treatment of hearing loss.