title: Magnetic resonance imaging of stem cell apoptosis in arthritic joints with a caspase activatable contrast agent.
abstract: 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 (1)H 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.
authors.affiliation: Department of Radiology and Molecular Imaging Program at Stanford (MIPS), Stanford School of Medicine , Stanford, California 94305, United States.
authors.forename: Hossein
authors.initials: H
authors.lastname: Nejadnik
authors.forename: Deju
authors.initials: D
authors.lastname: Ye
authors.forename: Olga D
authors.initials: OD
authors.lastname: Lenkov
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Donig
authors.forename: John E
authors.initials: JE
authors.lastname: Martin
authors.forename: Rostislav
authors.initials: R
authors.lastname: Castillo
authors.forename: Nikita
authors.initials: N
authors.lastname: Derugin
authors.forename: Barbara
authors.initials: B
authors.lastname: Sennino
authors.forename: Jianghong
authors.initials: J
authors.lastname: Rao
authors.forename: Heike
authors.initials: H
authors.lastname: Daldrup-Link
mesh_terms: D000818:Animals; D017209:Apoptosis; D001168:Arthritis / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D053148:Caspase 3 / Q000378:metabolism*; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006868:Hydrolysis; D007596:Joints / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
chemical_list: D003287:Contrast Media; D053148:Caspase 3
keywords: MRI; apoptosis; arthritis; molecular imaging; nanoparticles; stem cell