Stem-cell mediated therapy is a promising candidate for an extensive array of central nervous system (CNS) diseases including, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, stroke, and spinal cord injuries. The ability of stem cells to potentially regenerate non-dividing cells such as neurons holds great promise for the development of new therapies to restore damages caused by such debilitating diseases. Recent development of induced pluripotent stem cells (IPSC) further increased the societal viability of such therapeutic strategies by removing the ethical concerns inherent with embryonic stem cells (ESC). IPSCs are derived from cells that form the bodies of organisms as opposed to sperm or egg cells. They also offer the advantage of the possibility of being derived from the patients receiving the treatment, and therefore remove the risk of rejection, requiring no immunosuppressive drugs.
However, despite such great potential and the urgency of the calls for cure, the actual number of approved stem cell therapies to date remains insignificant. Primary reasons for this under-utilized potential include the highly varying therapy efficacy, and the possibility of serious side effects resulting from interference with normal CNS functions. One of the main difficulty lies in the fact that the CNS, mainly consisting of the brain, is a highly complex structure which consists of approximately 100 billion neurons and 300 billion cells supporting the function of these neurons with various cell types and dense connections. Without a way to precisely monitor how these stem cell transplantations perturb the complex CNS system, proper placement of these regenerating elements (stem cells) in the brain and spinal cord becomes an extremely difficult task.
In this proposal, we seek to provide a break-through in a search for the development of stem cell mediated therapies by developing a method to directly visualize the effects of the stem cell transplantation. This will be achieved by combining genetic techniques that will introduce modulatory capability to neural cells based on its cell type. We will strategically introduce capabilities for the underlying neural circuit as well as transplanted stem cells to be modulated by light. For stem cells, we expect our proposed technique to allow modulatory capability from only those developing into specific cell types. This cell-specific modulation capability will then combined with a novel imaging technique called passband b-SSFP fMRI, permitting non-invasive and high-resolution visualization of the regeneration processes. This project, upon its success, will provide direct functional assessment capabilities for the regenerated nerve tissue. This in turn will provide key guidance for developing novel stem cell therapies for CNS diseases.
Statement of Benefit to California:
Stem cell mediated therapy is a highly promising technology that gives us hope for a cure of many debilitating central nervous system (CNS) diseases that do not have an alternative for cure. With recent outstanding developments in stem cell biology, we are accelerating towards the search for a viable therapy. However, one of the main road blocks in developing a full blown therapy utilizing these advances in stem cell biology is the lack of tools to quantitatively monitor the direct effects of the stem cell transplantation. We seek to be instrumental in this search for a cure by introducing a completely novel way of directly assessing the functionality of stem cell driven neural circuitry in vivo. This project, upon its success, will allow accelerated development of novel stem cell therapies for a wide range of brain and spinal cord diseases that include Parkinson’s and Alzheimer’s disease, multiple sclerosis, stroke, and spinal cord injuries.
This technology will function as a bridge between the many outstanding efforts in stem cell biology and the development of stem cell mediated therapy, accelerating the search for a cure. Such accelerated development will not only provide help for many patients in urgent need for care in California, it will also greatly help the California economy by placing the state at the leading edge of the therapeutic method development. This technology will lead to accelerated search for new reagents, protocols, and technologies associated with cell therapy, which will stimulate the economy through patents, royalties, licensing fees, formation of new businesses, and adaptation of the technology by existing biotech companies, increasing California tax revenue and creating new jobs for Californians. The high impact of the proposed research will provide the much needed care for the Californians with debilitating diseases while holding a great promise for placing California at the leading edge of stem cell therapy and care.