Intra-Articular Injection of Synovium-Derived Mesenchymal Stem Cells with Hyaluronic Acid Can Repair Articular Cartilage Defects in a Canine Model

Abstract

Objective: The purpose of this study was to evaluate effectiveness of intra-articular injection of synovium-derived mesenchymal stem cells (SMSCs) and hyaluronic acid (HA) for the treatment of articular cartilage defects in a canine model. Methods: Forty-eight knees of 24 beagle dogs were randomly assigned to 16 groups (n=3) according to both the number of injected SMSCs (0.5×10 5 cells, 5×10 6 cells, 5×10 7 cells) and the concentration of HA (0%, 0.01%, 0.1%, 0.5%). A partial-thickness cartilage defect was created in the medial femoral condyle under arthroscopy. After seven weeks, autologous SMSCs with or without 1 ml HA were percutaneously injected into the injured knee. In the control group, 1 ml saline was injected. Twelve weeks after the injection, evaluation was performed using the International Cartilage Repair Society (ICRS) visual assessment scale and the modified O'Driscoll histological score. Results: The mean ICRS visual assessment scale and the mean modified O'Driscoll histological score were 1.0 ± 0.00 and 11.0 ± 0.00 in the control group. On the other hand, the mean ICRS visual assessment scale and the mean modified O'Driscoll histological score were 7.3 ± 3.21 and 30.7 ± 7.23 in the group injected with 5×10 6 cells and 0.01% HA. Conclusion: Intra-articular injection of SMSCs with HA may be effective for stimulating articular cartilage repair. Our results suggest that there is an ideal combination of the number of SMSCs and the concentration of HA for promoting articular cartilage repair.

The Effect of Intra-articular versus Intravenous Injection of Mesenchymal Stem Cells on Experimentally-Induced Knee Joint Osteoarthritis

“…These results are consistent with those of Miki et al . [ 36 ] study in which a surgically-induced cartilage defect was created in the medial femoral condyle of dogs’ knees. They found marked PGs accumulation and a considerable amount of chondrocyte-like cells after combined intra-articular injection of synovium-derived MSCs and hyaluronic acid 7 weeks postsurgery.…”

Review: Mesenchymal Stem Cell Therapy in Canine Osteoarthritis Research: “Experientia Docet” (Experience Will Teach Us)

“…The first type and majority of canine OA studies include companion animals suffering from naturally-occurring OA (Tables 1, 2, 3) (28,31,32,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(60)(61)(62). In studies of a second type, joint damage is induced in purpose-bred dogs in order to investigate the potential of MSCs to heal cartilage (Tables 4, 5) (51)(52)(53)(54)(55)(56)(57)(58)(59)63).…”

“…In studies based on OA models, cartilage or cranial cruciate ligament defects are created surgically in joints of purpose-bred dogs before MSC administration (51)(52)(53)(54)(55)(56)(57)(58)(59)63). In some studies, however, MSCs are administered during or immediately after surgery, which might not adequately represent the effect on chronic OA (52,53,(56)(57)(58).…”

Mesenchymal stem cells for cartilage regeneration in dogs

“…While in vitro studies provide a substantial amount of information about the potential of MSCs for cartilage repair, evaluation of the in vivo behavior and function of these cells is also required. In vivo studies of cMSCs for cartilage regeneration have involved the use of surgically induced cartilage defect models, including partial-thickness cartilage defect models[62,85-87] (Figure 4A), full-thickness cartilage defect models[88,89] (Figure 4B) and cranial cruciate ligament transection models[90]. (Table 3) In every model, intraarticular autologous[86-88] or allogeneic[51,63,89] cMSC injection demonstrated excellent regenerative effects, including hyaline-like cartilage regeneration, when compared with control groups.…”

“…Some studies have demonstrated greater repair effects, determined by histological evaluation of chondral defects, for intraarticular injections of cMSCs in combination with either hyaluronic acid[63,88] or platelet-rich plasma[90] when compared with injection of cMSCs alone. Therefore, some synergistic effects of cMSCs are expected when used in combination with chondroprotective materials.…”