Abstract
Background aims. Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. Methods. The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Results. Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Conclusions. Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs.
Acknowledgments
We thank Miyoko Ojima for her expert help with histology, Izumi Nakagawa for her management of our laboratory, and Toru Wakui, Minoru Yamada and Yoko Sekiyama in the pig center of Jichi Medical University for their expert support with preparing experiments and animal care.
This study was supported by “the Project for Realization of Regenerative Medicine” by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by “the Japanese Foundation for Research and Promotion of Endoscopy” to IS, by “the Global Center of Excellence (GCOE) Program” by MEXT to TM, and by “the Strategic Research Platform for Private Universities: Matching Fund Subsidy” by MEXT to EK.
Author contributions: TN, IS, TM and EK designed the experiments; TN and IS wrote the manuscript; TN performed experiments and collected and analyzed data; IS, TM and EK supervised the project and provided study materials and financial support; DH and MH assisted with the porcine experiment; KT proofread the manuscript; TK provided the GFP transgenic pig; AW performed magnetic resonance imaging, and analyzed data; SH, YF and HT provided and managed the pigs.
Disclosure of interests: The authors declare no competing interests.