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Richard Spencer, Ph.D., M.D., F.A.C.P., Senior Investigator Chief, Magnetic Resonance Imaging and Spectroscopy Section Laboratory of Clinical Investigation E-mail: spencer@helix.nih.gov Bibliography |
| Biography: Richard Spencer is Chief of the Magnetic Resonance Imaging and Spectroscopy Section of the National Institute on Aging of the National Institutes of Health in Baltimore, Maryland. He obtained his Ph.D. in Medical Physics from the Massachusetts Institute of Technology and his M.D. from Harvard Medical School. He was a postdoctoral fellow at the Francis Bitter National Magnet Laboratory of MIT before joining the NIH. He completed medical residency training at Johns Hopkins Bayview Medical Center in Baltimore and is a Diplomate of the American Board of Internal Medicine. |
| Tel: 410-558-8226; Fax: 410-558-8318 |
| Magnetic Resonance Imaging and Spectroscopy Section: The interests of the Magnetic Resonance Imaging and Spectroscopy Section are primarily in imaging (NMRI) and metabolic studies of three-dimensional cartilage grown from chondrocytes in culture with particular emphasis on biological response modifiers, and spectroscopic studies of cardiac and muscle metabolism under a variety of pharmacologic and physiologic conditions. Methodology development in magnetic resonance imaging and spectroscopy is also ongoing. |
| A Bioreactor System for Magnetic Resonance Microimaging and Spectroscopy of Chondrocytes and Neocartilage: Osteoarthritis is the leading cause of joint pathology in the older population. One approach to control this disease is the use of chondrocyte transplantation. Accordingly, we have begun a detailed exploration of cartilage growth and development in a hollow fiber bioreactor specially designed for NMR studies. This system permits cells and the three-dimensional matrix which they elaborate to be studied longitudinally for several weeks in a non-invasive manner. Ultimately, we hope to define appropriate conditions for neocartilage development in osteoarthritic joints in vivo. In addition, our work may aid in the development of tissue engineering protocols for cartilage tissue suitable for transplantation. |
| In cartilage developing from whole chick sterna, we have investigated the correlation between histology and NMR microimages. NMRI revealed the development of stromal layers between growth units of neocartilage centered about each hollow fiber. Density images show decreased mobile water content in these layers. Just outside the fiber walls, we find high proton density with relatively low mobility. Mobility increases with distance from the hollow fibers within the growth units, corresponding to differences in cell size and density. In magnetization transfer contrast images, we find that the lowest km values correspond to areas of high proteoglycan concentrations. These are prevalent in the mid-regions of the growth units. In contrast, the stromal layers and the regions around the fibers which are relatively proteoglycan-poor show the highest km values, potentially indicating greater collagen-water interactions. |
| We are also using 31P NMR to gain insight into metabolic adaptations as chondrocytes mature. We have been able to establish the presence of phosphocreatine in this system, and have demonstrated a decrease in intracellular pH during early development of the tissue. This is consistent with the known tendency for developing chondrocyte cartilage systems to become increasingly dependent on anaerobic metabolism. We have also found indirect evidence for a premineralization state of the tissue, characterized by a decrease in phosphate mobility. |
| In addition, we are investigating the effects of biologic response modifiers on neocartilage development. Using MRI, we have found that matrix proliferation from human articular chondrocytes is accelerated by addition of the combination of insulin like growth factor-1 (IGF-1) and transforming growth factor-b (TGF-b), or addition of the combination of IGF-1 and connective tissue growth factor, to the growth medium. Studies of the interactions of these growth factors and cytokines are ongoing. |
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