Osteoarthritis is a heterogeneous and multifactorial disease characterized by the progressive loss of hyaline articular cartilage. Recently, therapies that utilize autologous chondrocytes have been pursued, but the use of a patient’s own articular cartilage cells is quite limited. In pathological conditions where the body is unable to repair or regenerate tissue on its own, stem cell based therapeutic strategies have shown great promise. In particular, bone marrow derived mesenchymal stem cells (MSCs), a subset of adult stem cells, have demonstrated the ability to differentiate into a variety of cell lineages, including osteoblasts, adipocytes, chondrocytes, and myoblasts. Based on the ability to isolate these cells from patients, culture them ex vivo, and transplant them back into the body, adult stem cells are currently under investigation for their therapeutic potential in treating osteoarthritis.
The development of non-invasive imaging for assessing cell and tissue co-localizaton, cell migration, proliferation and therapeutic response will be critical for the success of future stem cell therapies. However, there are major challenges in the monitoring of these cells once administered in vivo. In order to visualize and track transplanted stem cells with MR imaging, cells have to be labeled with MR contrast agents. Initial cell labeling techniques have been hampered by a limited concentration of internalized contrast agents with subsequent limited sensitivity of MR to depict the labeled cells. In addition, the interaction between contrast agent-cell-scaffold becomes important in this case. New and improved methods need to be developed for efficient tracking of labeled cells, and ultimately the delivery and regenerative potential must be evaluated. In order to visualize and track transplanted stem cells with MR imaging, we propose the use of Micrometer-sized iron oxide (MPIO) particles as magnetic resonance contrast agents to track the fate of stem-cells non-invasively.
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 mesenchymal stem cells in regenerative medicine, is particularly important, as MSCs can be used for producing a wide variety of cell types 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 MSC transplantation for cartilage repair. This work will lead to novel therapeutic applications in tissue engineering and studies will potentially alleviate the cost of care in CA.
Training and Talent Development:
This proposal, with chemists, biologists, clinicians, and bioengineers focusing on non-invasive imaging for tracking stem cells, epitomizes an inter-disciplinary effort. This research as planned will include participation from graduate students, medical students, and post-doctoral researchers from multiple departments at UC San Francisco (UCSF). 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. 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 benefit is the common denominator for all of the above aspects. The rapid progress in inter-disciplinary science, the impact of the research on cartilage tissue engineering, the intellectual property potential, the enhanced national and international standing will all lead to economic benefits for CA.