Somatic Stem Cells as Vectors to Deliver Biologically Active Molecules to the Inn View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2009-2012

FUNDING AMOUNT

843333 USD

ABSTRACT

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-DC-102: Develop and Validate Methods for Delivery of Drugs and Molecules to the Inner Ear. The primary goal of this application is to establish and validate a robust, safe and long-lasting delivery method using somatic stem cells as vectors to transport biologically active molecules into the inner ear. Somatic stem cells, such as mesenchymal stem cells and induced pluripotent stem cells represent a promising source of material for autologous cell transplantation therapies. While these stem cells can be used to replace damaged cells in the inner ear, our recent study has demonstrated that transplanted somatic stem cells exhibit remarkable abilities to identify and migrate towards damaged spiral ganglion neurons in the inner ear. This property makes somatic stem cells a unique tool to deliver therapeutic agents selectively to damaged cells in the inner ear. In Specific Aim 1, we will establish mesenchymal and induced pluripotent stem cell lines stably expressing high-level BDNF. Release of BDNF from individual stem cells in vitro will be quantitatively evaluated by innovative single cell immunoblot assays. In Specific Aim 2, mesenchymal or induced pluripotent stem cells releasing BDNF will be transplanted into the cochlea of an animal model of auditory neuropathy. Migration and engraftment of these stem cells in vivo will be monitored by a high-resolution microscopic- endoscope-based imaging system and magnetic resonance imaging. In addition, temporal changes in BDNF release from transplanted stem cells in vivo will be evaluated by a combination of fluorescence-activated cell sorting and Western blot analysis. Together, these experiments will provide the first comprehensive set of information regarding the feasibility of using autologous somatic stem cells to deliver therapeutic agents into the inner ear, and thus have significant clinical implications. The inner ear contains complex and sensitive structures, which present a significant challenge for therapeutic interventions. We propose to advance the feasibility of a novel method using patient-derived stem cells to deliver therapeutic agents to the inner ear, with the long-term goal of benefitting a large proportion of patients suffering from profound sensorineural hearing loss. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=7933801

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