Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

Abstract

IntroductionThe purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs) with low molecular weight hyaluronic acid (HA) could promote regeneration of massive cartilage in rabbits.Material and methodsThe SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek). The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml) were suspended in 0.5% low molecular weight HA (0.15 ml) and injected into the left knee, and HA solution (0.30 ml) alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days.ResultsOn day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC-treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage.ConclusionThus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

Hyaluronic Acid Supplement as a Chondrogenic Adjuvant in Promoting the Therapeutic Efficacy of Stem Cell Therapy in Cartilage Healing

“…In the current study, we found that the combinatory use of BMSCs and HA improves the cartilaginous healing of chondral defects, both macroscopically and microscopically. The results were in line with other stem-cell-based injection studies with rat, rabbit, and canine models [ 17 , 18 , 19 ]. Interestingly, most studies consistently reported the superior efficacy of combined BMSCs and HA on chondral defect healing than that of isolated stem cells or HA alone.…”

“…Unlike conventional treatment modalities, which need open surgery for cells or scaffold transplantation, direct stem cell injection emerges as a simple, minimally invasive, and attractive therapeutic approach for treating chondral defects in recent years. Moreover, many studies have reported promising results of stem-cell-based injection therapy in promoting cartilage repair and regeneration [ 12 , 13 , 17 , 18 , 20 , 29 , 30 , 31 , 33 ]. Mcllwraith et al showed that full-thickness chondral defects in an equine model treated with microfracture followed by IA BMSC injection have superior outcomes than microfracture alone [ 32 ].…”

“…Additionally, under appropriate culture conditions, stem cells can be expanded in vitro while maintaining their chondrogenic potential [ 16 ]. Several studies have demonstrated the efficacy of intra-articular (IA) injection of cultured BMSCs in promoting healing of chondral defects, not only in preclinical animal studies, but also in pilot human clinical trials [ 17 , 18 , 19 , 20 , 21 ].…”

Characteristic features of newly established specific pathogen-free albino large rabbit (JW-AKT): Comparison with Japanese White and New Zealand White rabbits

“…Thus, JW-AKT rabbits could serve as an alternative candidate for an animal model to replace dogs because of their body size and easiness in handle. The larger rabbit (including Flemish giant) models have been employed for medical research with surgical treatments especially in vascular [2, 9, 17] and orthopedic [3,4,5, 12, 13, 23] experiments. Additionally, large body size is advantageous in collection of a large amount of biological specimen.…”

“…Larger rabbit (including Flemish giant) models have been employed for medical research, especially in those that involved surgical treatment including vascular [2, 9, 17] and orthopedic [3,4,5, 12, 13, 23] surgery due to its body size. Because of recent greater animal welfare advocacy for the ethical treatment, it is getting harder to use dogs as an experimental animal [19].…”