Abstract
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.
Highlights
To advance the field of cartilage regeneration, it is necessary to understand the natural progression of repair before potential therapeutic targets can be identified
Synovial MSCs from MRL mice may demonstrate increased cartilage repair capacity compared to C57BL6 mice, since synovial stem/progenitor cells have increased in vitro chondrogenic capacity when compared to bone marrow stem/progenitors[26,27]
In this study we first characterized which cell populations were involved in endogenous cartilage healing in MRL mice and transplanted these cells into C57BL6 non-healing mice to observe if MRL “superhealer” progenitor cells were capable of promoting increased regenerative capacity of articular cartilage
Summary
To advance the field of cartilage regeneration, it is necessary to understand the natural progression of repair before potential therapeutic targets can be identified. At 4 and 8 weeks, MRL mice appear to be protected from the morphological changes that occur in the C57BL6 mice in response to traumatic injury. It is important to note that in both the Ward et al.[23] study and Fitzgerald[22] study, only morphological changes were observed and no attempt was made to elucidate the repair response at a cellular level: if stem cells and/or immune cells (such as macrophages) are playing any role in the enhanced regeneration in MRL mice. The authors investigated whether intra-articular transplantation of bone marrow-derived MSCs from MRL mice were superior in slowing down the post-traumatic arthritis compared to bone marrow-derived MSCs from C57BL6 mice[25]. In this study we first characterized which cell populations were involved in endogenous cartilage healing in MRL mice and transplanted these cells into C57BL6 non-healing mice to observe if MRL “superhealer” progenitor cells were capable of promoting increased regenerative capacity of articular cartilage
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