Effectiveness of tibial plateau leveling osteotomy (TPLO) and intra-articular inoculation od AD-MSC and hyaluronic acid in the treatment of ostheoarthritis secondary to rupture of the cranial cruciate ligament in dogs.

To assess the evolution of OA in the stifle of dogs with CCL tear and treated with TPLO with and without intra-articular injection of AD-MSC (adult mesenchymal stem cells derived from fat) and hyaluronic acid (HA). Eleven dogs, 9 f, 2 m, mean age 4.4 y (1.5-9) and mean weight 35 kg (19-75), with a CCL tear underwent TPLO (T0) and were given injections of AD-MSC (2 mln/ml) and HA (20mg) (group1:8 dogs) or not (group 2: 3 dogs).Control visits were performed at 15, 30 (T1), 60 (T2) days.t T0, T1 and T2 the degree of radiographic OA using the Kellgren-Lawrence scale was assessed.At T0 and T2 an SF sample, which has been tested for mucin, chemical-physical, cytological, and microbiological analysis, was taken. No dogs had problems either during surgery or in the postoperative period. At 60 days after surgery (T2), 10 dogs showed full functional recovery of the treated limb. In Group 1: The degree (g) of radiographic OA was classified at T0: 0 g in 4 cases; 1 g in 1 case,3 g in 1 case, 4 g in 2 cases; at T1: 0 g in 4 cases, 1 g in 1 case, 3 g in 1 case,  4 g in 2 cases; at T2: 0 g in 4 cases; 2 g in 1 case, 3g in 1 case and 4 g in 2 cases. At T0, the analysis of SF showed: chronicactive immune-mediated arthritis (1 case), mild chronic synovitis (5 cases), hemarthrosis (2 cases); at T2:all dogs showed an improvement in the quality and quantity of SF. In Group 2, At T0: 1 case had 0 g of OA and 2 cases grade 2;at T1: 0 g in 1 case and 2g in 2 cases; at T2: g 1 in 1 case, g 3 in 2 cases. At T0, the analysis of SF showed: mild chronic synovitis (2 cases), chronicactive immune-mediatedarthritis (1 case); at T2: all dogs showed an improvement in the quality and quantity of SF. These data support the literature regarding the usefulness of an early stabilization of the stifle with TPLO, following CCL rupture. It is known that no surgery can stop the progression of arthrosis. In this regard, some differences emerged between the group treated with AD-MSC and that not treated. All 8 group 1 dogs, had no progression of OA at T1 and at T2 only1 case had progression of OA. All 3 dogs of group 2, however, showed progression of OA at T2. It can, therefore, be assumed that the intra-articular injection of AD-MSC and HA contributes to reduce the progression of OA, particularly in those patients who are treated before the onset of joint damage. Our findings on cytology SF are in line with thosereported by Doom and, in addition, we also found a decrease of GAG in the earlystages of OA, a dilution of HA with loss of viscosity of the SF, asreported by Caterson. At 60 days after surgery,in allsubjects an increase of GAG was found. The finding that treatment with AD-MSC was always well-tolerated and that a delay in the onset or progression of OA is constantly verified. It is assumed that, in addition to their well-known regenerative features, AD-MSC , play an important role in the control of articular inflammation. A longer observation period and further case histories will allow more accurate evaluations. Our studies are currently aimed at assessing other elements of the SF, such as cytokines IL-1, IL-6 and TNF; MMP-3, TIMPs, KS-5D4,COMP.