Xie Meihua, Luo ShuLin, Li Ying, Lu Laiya, Deng Cuijun, Cheng Yu, Yin Feng
Institute for Regenerative Medicine, The Institute for Biomedical Engineering & Nano Science, Shanghai East Hospital, Tongji University School of Medicine 1800 Yuntai Road Shanghai 200123 China
Department of Joint Surgery, Shanghai East Hospital, School of Medicine, Tongji University Shanghai China
RSC Adv. 2019 Apr 16;9(21):12010-12019. doi: 10.1039/c8ra09570a. eCollection 2019 Apr 12.
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 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 ( of 184 mM s) 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 maps showed a persistence time of the IO-CS nanoparticles in ADSCs of 6 days . Then, we investigated the imaging capability of the IO-CS nanoparticle-labeled ADSCs 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 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.
脂肪来源干细胞（ADSCs）因其多能性和易于获取，在软骨组织工程中具有巨大潜力。磁共振成像（MRI）是一种有效且无创的成像方法，可用于追踪细胞并观察新组织再生。找到一种不影响ADSCs干性的兼容且高效的成像试剂至关重要。在此，我们开发了壳聚糖修饰的氧化铁纳米颗粒（IO-CS）作为具有良好细胞兼容性和高细胞摄取效率的造影剂，并将IO-CS用于大鼠骨关节炎（OA）模型的ADSC关节内成像。透射电子显微镜（TEM）显示IO-CS纳米颗粒具有良好的形态和尺寸分布，尺寸为17纳米。磁化强度（每克29.4电磁单位）和MRI测试证实（弛豫率为184 mM s）IO-CS纳米颗粒作为MRI造影剂的可行性。此外，与商业试剂 ferumoxytol相比，IO-CS纳米颗粒显示出良好的细胞兼容性和高标记效率。而且，IO-CS纳米颗粒的掺入并未改变ADSCs的成脂、成骨和软骨形成分化能力。此外，MRI横向弛豫率图谱显示IO-CS纳米颗粒在ADSCs中的持续时间为6天。然后，我们用MRI研究了IO-CS纳米颗粒标记的ADSCs的成像能力，为期5周。组织学研究证明了IO-CS纳米颗粒在关节内的生物分布，包括软骨表层、滑膜下层、骨膜和骨髓腔。它们提供了OA大鼠模型中ADSCs的全身分布信息。总之，我们开发了一种易于获取且有效的成像试剂，具有良好的生物相容性并能维持ADSCs的干性。这表明IO-CS纳米颗粒作为MRI试剂在软骨组织工程中具有潜在的转化应用价值。
