Synovium-Derived Mesenchymal Stem Cells in Combination with Low Molecular Weight Hyaluronic Acid for Cartilage Repair

Abstract

Regeneration of damaged articular cartilage remains one of the most complex and unresolved problems in traumatology and orthopedics. In this study, we investigated whether intra-articular injection of synovium-derived mesenchymal stem cells (SD-MSCs) with low molecular weight hyaluronic acid (LMWHA) could promote the regeneration of damaged cartilage in rabbits. To answer this question, rabbits' SD-MSCs were harvested, expanded in culture, and characterized by CFU assay and a multilineage differentiation test. For in vivo study, we created a defect within the cartilage layer without destroying subchondral bone. Two weeks after the cartilage defect, SD-MSCs (2×106 cells) were suspended in 0.5% LMWHA and injected into the left knee, and hyaluronic acid (HA) solution alone was placed into the right knee. Cartilage regeneration in experimental and control groups was evaluated macroscopically and histologically at Days 30, 60, and 90. The results of the study showed an early process of cartilage regeneration in the defect area on Day 30 after intra-articular MSCs-HA injection. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chondroblasts, in contrast to a single HA injection, which did not induce cartilage regeneration. On Day 60, we observed that the size of the cartilage defect after MSCs-HA injection significantly decreased, compared to one after HA injection. On Day 90, the cartilage defect in a knee treated with MSCs-HA was fully regenerated and was similar to intact cartilage. Thus, the combined application of the MSCs, HA, and chondroinductive proteins have a high therapeutic effect on cartilage defect regeneration in rabbits.