Gerald D. Aurbach Memorial Lecture
Friday, October 12 / 8:15 am – 9:15 am
Prospects for Therapies with Adult Stem/Progenitor Cells (MSCs) or the Proteins They Produce
Darwin J. Prockop, M.D., Ph.D., Texas A&M Health Science Center College of Medicine (USA)
Therapeutic benefits in a number of models for human disease have been reported with administration of the adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or mesenchymal stromal cells (MSCs). We observed that intravenously administered MSCs improved myocardial infarction in mice by being trapped in the lung where they created microemboli that activated the cells to synthesize TSG-6, and the TSG-6 reduced the excessive inflammatory response that damaged cardiomyocytes (Lee et al. Cell Stem Cell 2009). We also observed that intraocular administration of TSG-6 reduced the excessive inflammatory response that damaged the cornea in a rodent model for chemical injury of the eye (Oh et al. PNAS 2010).
In parallel experiments we observed that retinal degeneration was decreased in a rat model for retinitis pigmentosa by intravitreal administration of STC-1 (Roddy et al. Molecular Therapy, 2012), an anti-apoptotic protein produced by hMSCs in response to signals from apoptotic cells (Block et al. Stem Cells 2009). However, in a model for regeneration of rat meniscus, hMSCs engrafted for several weeks and enhanced regeneration in part by being activation to express genes that are expressed during endochondrial ossification: Ihh, BMP-2 and PTHLH (Horie et al. under review). The results indicate that some of the therapeutic benefits observed with administration of MSCs in disease models can be duplicated by administration of therapeutic factors the cells produce such as TSG-6 or STC-1. However, other beneficial effects are apparently explained by more complex interactions between the cells and the microenvironments created by injuries to specific tissues.
About Dr. Darwin Prockop
Darwin J. Prockop, M.D., Ph.D., is the Director of the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White in Temple, TX. He has done research on collagen biosynthesis, mutations causing skeletal disorders and, more recently, on adult stem/progenitor cells from bone marrow referred to as mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). The efforts of his research group have focused on both the basic biology of MSCs and their potential therapeutic uses in diabetes, and in diseases of the lung, heart, central nervous system and skeletal system. In addition, plans are being developed to use the cells in clinical trials in patients. Dr. Prockop has published over 500 papers in reviewed journals. He has received four honorary degrees and he is a member of the National Academy of Sciences and the Institute of Medicine.
Louis V. Avioli Memorial Lecture
Saturday, October 13 / 8:00 am – 9:00 am
Advanced Bone Imaging in Osteoporosis: Monitoring Disease Progression, Predicting Fracture Risk, and Providing Surrogacy for Fracture Outcome – the “Holy Cow!” or the “Holy Grail?”
Harry K. Genant, M.D., University of California, San Francisco and CCBR-SYNARC, Inc. (USA)
The skeleton is comprised of cortical and trabecular bone, each contributing to skeletal strength and to fracture resistance. The determination of skeletal status in health and disease, and its response to therapy and propensity to fracture have been primarily based on assessment of standard bone mineral density (BMD) and mass (BMC) by areal or volumetric X-ray-based imaging techniques. While such BMD/BMC evaluations by dual-X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) have clinical utility in detecting bone loss and diagnosing osteoporosis, they do not fully assess the impact of metabolic disorders or therapeutic interventions on the skeleton or adequately predict the risk of appendicular and axial fractures. Additionally, these standard bone density techniques have not achieved regulatory recognition as valid surrogates for fracture outcome.
As a consequence, there has been considerable interest in the examination of other factors beyond BMD associated with bone integrity and mechanical competence, including the macro and micro-structure and strength of both cortical and trabecular bone and the basic composition of skeletal tissue. The analysis of bone morphology including micro-architecture and ultra-structure of the trabecular and cortical compartments has been accomplished using the remarkable, high-resolution imaging capabilities of advanced computed tomography (CT), micro-computed tomography (μCT) and magnetic resonance (MR) systems, combined with advanced image processing and computational approaches, including finite element analysis (FEA) for estimating bone strength.
These newer advanced imaging technologies now have been widely applied in pre-clinical and clinical research and have contributed enormously to our understanding of the complex relationships among bone density, mass, geometry, micro-structure, strength and fracture propensity, across a range of axial and appendicular skeletal sites, and their variable cortical, trabecular and endosteal or endocortical components. The skeletal consequences of aging, disease progression and response to novel therapy have been extensively examined and considerably illuminated through application of these advanced bone imaging and analysis methods. The results of these studies have propelled us well beyond the mere realm of spectacular images, the “Holy Cow!”, to an exalted sphere of enhanced skeletal structural knowledge approaching, albeit not yet attaining, the “Holy Grail.”
About Dr. Harry Genant
Harry K. Genant, M.D., is Professor Emeritus of the University of California San Francisco, and Member of the Board of Directors of CCBRSYNARC, Inc. He founded the Osteoporosis and Arthritis Research Group (OARG) in the Department of Radiology, UCSF, and served as its Executive Director. In 1998 he co-founded Synarc, Inc., a global, contract research organization (CRO) specializing in management of quantitative imaging and biomarkers in large, multicenter, multinational, pharmaceutical drug trials. Dr. Genant has been editor or co-editor of more than 30 books and author or co-author of more than 170 chapters or invited articles, more than 600 articles in peer-reviewed scientific and medical journals, and more than 1500 abstracts presented at national and international scientific and professional gatherings. He is on the editorial boards of Osteoporosis International and the Journal of Clinical Densitometry, and is Associate Editor of Bone.