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Magnetic Resonance Imaging of Stem Cell Apoptosis in Arthritic Joints with a Caspase Activatable Contrast Agent

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journal contribution
posted on 24.02.2015, 00:00 by Hossein Nejadnik, Deju Ye, Olga D. Lenkov, Jessica S. Donig, John E. Martin, Rostislav Castillo, Nikita Derugin, Barbara Sennino, Jianghong Rao, Heike Daldrup-Link
About 43 million individuals in the U.S. encounter cartilage injuries due to trauma or osteoarthritis, leading to joint pain and functional disability. Matrix-associated stem cell implants (MASI) represent a promising approach for repair of cartilage defects. However, limited survival of MASI creates a significant bottleneck for successful cartilage regeneration outcomes and functional reconstitution. We report an approach for noninvasive detection of stem cell apoptosis with magnetic resonance imaging (MRI), based on a caspase-3-sensitive nanoaggregation MRI probe (C-SNAM). C-SNAM self-assembles into nanoparticles after hydrolysis by caspase-3, leading to 90% amplification of 1H MR signal and prolonged in vivo retention. Following intra-articular injection, C-SNAM causes significant MR signal enhancement in apoptotic MASI compared to viable MASI. Our results indicate that C-SNAM functions as an imaging probe for stem cell apoptosis in MASI. This concept could be applied to a broad range of cell transplants and target sites.