Browsing by Author "Mak, J."

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    Evaluating endogenous repair of focal cartilage defects in C57BL/6 and MRL/MpJ mice using 9.4 T magnetic resonance imaging: A pilot study
    (Elsevier, 2015-01-09) Mak, J.; Leonard, C.; Foniok, T.; Rushforth, D.; Dunn, Jeffrey F.; Krawetz, R.
    The use of magnetic resonance imaging (MRI) for evaluating joint injuries is often considered superior to radiography due to the capacity of MRI for visualizing both soft and hard tissues. While longitudinal studies regarding cartilage repair have been undertaken on patients and in larger animal models, a method has yet to be developed for mouse cartilage to be repeatedly and non-invasively evaluated over time. The aim of this pilot study was to investigate if morphological changes following a focal cartilage injury in mice could be measured by 9.4T magnetic resonance imaging. Focal cartilage defects were induced in the left knee of 4-6weeks old C57BL/6 and MRL/MpJ mice. At endpoints 0, 2, and 4weeks post-injury, legs were dissected out and imaged ex vivo. The defect could be detected by MRI immediately after injury, appearing as a hyperintense focal point and with size similar to that of the surgical tool used. Defects were visible in both strains up to 4weeks post-injury, although signal intensity decreased over time. One C57BL/6 in particular, displayed extensive fibrosis in the patellar tendon at 4weeks as assessed by histology, while the MR images of the same animal displayed a clear, structural distinction between the patella and the new tissue growth. Overall, our results suggest that MRI could be used for longitudinal studies in murine cartilage injury models to evaluate certain characteristics of repair not detectable through histology.
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    Intra-articular injection of synovial mesenchymal stem cells improves cartilage repair in a mouse injury model
    (Nature Publishing Group, 2016-03-17) Mak, J.; Jablonski, C. L.; Leonard, C. A.; Dunn, Jeffery F.; Raharjo, E.; Matyas, J. R.; Biernaskie, J.; Krawetz, R. J.
    Controversy remains whether articular cartilage has an endogenous stem/progenitor cell population, since its poor healing capacity after injury can lead to diseases such as osteoarthritis. In the joint environment there are mesenchymal stem/progenitor cells (MSCs) in the synovial membrane and synovial fluid that can differentiate into cartilage, but it is still under debate if these cells contribute to cartilage repair in vivo. In this study, we isolated a Sca-1 positive, chondrogenesis capable population of mouse synovial MSCs from C57BL6 and MRL/MpJ “super-healer” strains. Intra-articular injection of Sca-1 + GFP + synovial cells from C57BL6 or MRL/MpJ into C57BL6 mice following cartilage injury led to increased cartilage repair by 4 weeks after injury. GFP expression was detected in the injury site at 2 weeks, but not 4 weeks after injury. These results suggest that synovial stem/progenitor cells, regardless of strain background, have beneficial effects when injected into an injured joint. MSCs derived from MRL/MpJ mice did not promote an increased repair capacity compared to MSCs derived from non-healing C57BL6 controls; however, MRL/MpJ MSCs were observed within the defect area at the time points examined, while C57BL6 MSCs were not.