Abstract
Adipose-derived stem cells (ADSCs) hold great potential in cartilage tissue engineering due to their multipotency and ease of availability. MRI is an effective and noninvasive imaging approach to track cells and observe new tissue regeneration. It is essential to find a compatible and efficient imaging reagent without affecting the stemness of ADSCs. Herein, we developed chitosan-modified iron oxide nanoparticles (IO-CS) as the T2 contrast reagent with good cell compatibility and high cellular uptake efficiency and used IO-CS for ADSC intra-articular imaging in a rat osteoarthritis (OA) model. TEM demonstrated the great morphology and size distribution of IO-CS nanoparticles with the size of 17 nm. Magnetization (29.4 emu per g) and MRI tests confirmed (R2 of 184 mM−1 s−1) the feasibility of IO-CS nanoparticles as an MRI contrast reagent. In addition, the IO-CS nanoparticles showed good cellular compatibility and high labeling efficiency as compared to the commercial agent ferumoxytol. Moreover, incorporation of IO-CS nanoparticles did not alter the adipogenic, osteogenic and chondrogenic differentiation ability of ADSCs. Furthermore, the MRI transverse R2 maps showed a persistence time of the IO-CS nanoparticles in ADSCs of 6 days in vitro. Then, we investigated the imaging capability of the IO-CS nanoparticle-labeled ADSCs in vivo with MRI for 5 weeks. The histological studies demonstrated the intra-articular biodistribution of the IO-CS nanoparticles, including in the cartilage superficial layer, synovial sublining layer, periosteum and bone marrow cavity. They provided systemic distribution information of the ADSCs in the OA rat model. In summary, we developed an accessible and effective T2 imaging reagent with good biocompatibility and maintenance of the stemness of ADSCs. This showed the potential translational application of IO-CS nanoparticles as an MRI reagent in cartilage tissue engineering.
Highlights
Osteoarthritis (OA) is the most common degenerative joint disease and still far from cure
iron oxide nanoparticles (IO-CS) nanoparticles showed a decrease in saturation magnetization, the nanoparticles could still be efficiently separated from the medium
There was no signi cant difference between the iron oxide (IO)-CS nanoparticles labeled group and the control group from alizarin red staining and toluidine blue staining. These results demonstrated that IO-CS nanoparticles did not hinder the adipogenic, osteogenic or chondrogenic differentiation potential of Adipose-derived stem cells (ADSCs), which were consistent with other reports.[22]
Summary
Osteoarthritis (OA) is the most common degenerative joint disease and still far from cure. Stem cell therapy is widely applied in tissue regeneration,[1,2] cancer treatment[3,4] and wound healing.[5] This stimulates researchers to restore diseased articular cartilage in OA patients via stem cell therapy.[1,6] some studies have demonstrated the effectiveness and potential of stem cell therapy in OA cartilage regeneration, to date, there is a lack of tools for tracking the stem cells. The periods of observation ranged from 5 weeks to 10 weeks, and clinical trials could last for years or even longer.[14,15,16] Still, it is urgent to develop a safe, long-term and effective imaging reagent for stem cells in the treatment of OA cartilage
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