Monitored Systemic Delivery Of HESC to Pathological Organs

Funding Type: 
Comprehensive Grant
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Degenerative diseases, such as Parkinson’s, Alzheimer’s and muscle atrophy, in which the bodies capacity to regenerate new tissue can no longer keep up with tissue death are debilitating for individuals and represent a major problem for society. Transplantation therapy based on the use of human embryonic stem cells (hESCs) and their tissue derivatives is thought to provide clinical help for these incurable disorders. At the same time, there are no known methods for deliberate targeting of transplanted cells to pathological tissues; and more importantly, such methods cannot be successfully developed in humans without first establishing non-invasive imaging technology for monitored optimization of transplantation procedures and for the assessment of stem cell behavior in living tissue. Hence, even if the tissue-specific differentiation of hESCs is achieved, the development of effective therapies for degenerative disorders critically requires much improved methodology for targeted delivery of transplanted cells to the organs in need for repair.
This proposal is focused on development of new interdisciplinary technology bridging biomedical imaging, stem cell manipulations and regenerative medicine with the goal to improve the cell transplantation techniques and to create non-invasive methods for monitored regeneration of injured or pathological skeletal muscle by transplanted derivatives of human embryonic stem cells. This work will yield valuable pre-clinical data and will enable transition to clinical studies focused on the non-invasive monitored enhancement of tissue repair in the old and those afflicted by debilitating degenerative disorders. Specifically, this research plan pursues the development of non-invasive imaging methods for monitored optimized delivery of stem cells to skeletal muscle and for enhancement of regenerative responses in through the following logical steps:
1. Establishing designer hESC lines which could be targeted to injured of pathological tissues.
2. Developing non-invasive imaging methods to monitor and optimize the visualization of the designer hESC lines, in culture and in muscle explants, thus generating data for the in vivo experiments.
3. Developing non-invasive imaging methods to monitor and optimize the targeted delivery of hESCs to muscle regenerating after injury or during chronic dystrophic pathology, in vivo.

The ultimate goal is to enable optimal repair of pathological organs by transplanted derivatives of hESC by using the targeted delivery to injured or pathological tissues independently of the hESC origin, methods of derivation and line-to-line variations. Due to the “ambitious” nature of this project and the necessity to use non-NIH registered hESC lines, this proposal has no realistic possibility to be funded by federal government.

Statement of Benefit to California: 

This proposal has significant benefit for the advancement of science, education, national and global visibility and economy for the state of California, (CA). Research and Scientific Benefit: The use of human embryonic stem cells (hESCs) in regenerative medicine, is particularly important, as hESCs can be used for producing any cell-type, such as neuronal, muscle, etc. and used to replace their dysfunctional counterparts in living humans. The key obstacle to stem cell therapy is the inability to track the cells and their fate through the body, non-invasively. This study will create novel non-invasive magnetic resonance imaging for monitoring the success of hESC transplantation in individuals with muscle degenerative disorders. This will lead to novel therapeutic applications in muscle atrophy, caused by old age, stroke, immobility, muscular dystrophies, etc.. With an aging society, these studies will potentially alleviate the cost of care and the societal burden of aging in CA. Training and Talent Development: This proposal, with stem-cell biologists and engineers focusing on non-invasive imaging for tracking stem cells in muscle regeneration, epitomizes an inter-disciplinary effort. This research as planned will include participation from {REDACTED} and broader possibilities of collaboration with foreign institutions. This will provide unique hands-on training, supplementing text-book teaching, and motivating a diverse and large number of individuals in CA, and lead to future funding from diverse sources. National and Global Standing: CA has taken leadership and is one of the few states investing resources in Stem Cell research. The science proposed here would potentially bring investments from institutions in other states. The technology transfer potential from researchers in institutions in states not as progressive as CA, represents a new paradigm with significant financial gains for the future. Collaborations with countries such as South Korea, Japan and France, as planned in this proposal, via the process of recruiting post-doctoral researchers, holds promise for intellectual cross pollination at the global level. This will lead to an influx of researchers and scientists into the CA area, and may also lead to foreign company investments in the CA economy where they will find the right talent. The diversity and outreach efforts of the team and the institutions are well known and will lead to rapid dissemination of the science and research to the public. Financial: Financial benefit is the common denominator for all of the above aspects. The rapid progress in inter-disciplinary science, the impact of the research on disorders of the muscle, the intellectual property potential, the enhanced national and international standing will all lead to economic benefits for CA.