Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and suggests anti-inflammatory mechanism of action

Autoři: Amanda M. Hamilton aff001;  Wing-Yee Cheung aff002;  Alejandro Gómez-Aristizábal aff002;  Anirudh Sharma aff002;  Sayaka Nakamura aff002;  Amélie Chaboureau aff002;  Shashank Bhatt aff002;  Razieh Rabani aff002;  Mohit Kapoor aff002;  Paula J. Foster aff001;  Sowmya Viswanathan aff002
Působiště autorů: Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada aff001;  The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada aff002;  Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON, Canada aff003;  Department of Surgery, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada aff004;  Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada aff005;  Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada aff006;  Department of Medicine, University of Toronto, Toronto, ON, Canada aff007
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0214107


Osteoarthritis (OA) is characterized by cartilage degradation and chronic joint inflammation. Mesenchymal stem cells (MSCs) have shown promising results in OA, but their mechanism of action is not fully understood. We hypothesize that MSCs polarize macrophages, which are strongly associated with joint inflammation to more homeostatic sub-types. We tracked ferumoxytol (Feraheme, iron oxide nanoparticle)-labeled murine MSCs (Fe-MSCs) in murine OA joints, and quantified changes to joint inflammation and fibrosis. 10-week-old C57BL/6 male mice (n = 5/group) were induced to undergo osteoarthritis by destabilization of medical meniscus (DMM) or sham surgery. 3 weeks post-surgery, mice were injected intra-articularly with either fluorescent dye-(DiR) labeled or DiR-Fe-MSC or saline to yield 4 groups (n = 5 per group for each timepoint [1, 2 and 4weeks]). 4 weeks after injection, mice were imaged by MRI, and scored for i) OARSI (Osteoarthritis Research Society International) to determine cartilage damage; ii) immunohistochemical changes in iNOS, CD206, F4/80 and Prussian Blue/Sca-1 to detect pro-inflammatory, homeostatic and total macrophages and ferumoxytol -labeled MSCs respectively, and iii) Masson’s Trichrome to detect changes in fibrosis. Ferumoxytol-labeled MSCs persisted at greater levels in DMM vs. SHAM-knee joints. We observed no difference in OARSI scores between MSC and vehicle groups. Sca-1 and Prussian Blue co-staining confirmed the ferumoxytol label resides in MSCs, although some ferumoxytol label was detected in proximity to MSCs in macrophages, likely due to phagocytosis of apoptotic MSCs, increasing functionality of these macrophages through MSC efferocytosis. MRI hypertintensity scores related to fluid edema decreased in MSC-treated vs. control animals. For the first time, we show that MSC-treated mice had increased ratios of %CD206+: %F4/80+ (homeostatic macrophages) (p<0.05), and decreased ratios of %iNOS+: %F4/80+ macrophages (p<0.01), supporting our hypothesis that MSCs may modulate synovial inflammation.

Klíčová slova:

Inflammation – Knee joints – Knees – Macrophages – Magnetic resonance imaging – Mesenchymal stem cells – Osteoarthritis – Skeletal joints


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2019 Číslo 12