The therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells implantation on knee osteoarthritis / 中华老年医学杂志

ABSTRACT

Objective To explore the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells(UC-MSCs)implantation on knee osteoarthritis(OA)in rabbits. Methods The healthy adult New Zealand rabbits were divided into control group(n=4),OA model group(n=4),and treatment group(n= 4).OA model was induced by 4% papain injection(0.1 ml/kg for 2 times),and treatment group were treated with UC-MSCs implantation(1 ml,1×105/L).At 2 weeks after papain injection for preparation of osteoarthritis model,rabbits knee joints were examined by MRI,and synchrony serum levels of IL-6 and-8,MMP-3 and-13 were tested.At 3 weeks after papain injection for OA,1×106/L 1 ml UC-MSCs were injected into articular cavity in treatment group,and normal saline was injected into articular cavity in blank control group and OA model group.At 2 weeks and 4 weeks after the treatment,serum levels of IL-6 and IL-8,MMP-3 and MMP-13 were tested respectively.At 4 weeks after the treatment,knee joints were reexamined again by MRI.After this,the rabbits were sacrificed and synovium and articular cartilage were taken out for HE and immunohistochemistry examination.Serum levels of IL-6 and IL-8,MMP-3 and MMP-13 were tested by ELISA method. Results The levels of inflammatory cytokines such as IL-6,IL-8,MMP-3,MMP-13 were significantly higher in model group 〔(44.7 ± 14.5)μg/L,(7.6 ± 2.5)μg/L,(16.5 ± 4.3)μg/L,(4.50 ± 1.20)μg/L〕and in treatment group 〔(43.9 ± 15.2)μg/L,(9.8 ± 2.9μg/L),(18.3 ± 4.9) μg/L,(4.80 ± 1.80)μg/L〕than in control group〔(20.8 ± 11.2)μg/L,(1.2 ± 0.6)μg/L,(2.8 ± 0.9) μg/L,(0.02 ± 0.02)μg/L〕(all P < 0.05).The levels of IL-6,IL-8,MMP-3,MMP-13 were significantly lower after UC-MSCs treatment〔(23.8 ± 11.4)μg/L,(2.4 ± 1.3)μg/L,(10.5 ± 3.4)μg/L,(0.50 ± 0.20)μg/L〕than before treatment(all P<0.05).Based on magnetic resonance imaging,the treatment group versus model group showed an improved coarse cartilage surface,thickened subchondral bone and synovium,and decreased volume of joints effusion.Pathological finding showed lower levels of inflammatory reaction in cartilage and synovium in the treatment group versus model group.Immunohistochemistry showed lower levels of IL-6 and MMP-13(all P<0.05). Conclusions The inflammatory response of cartilage and synovial tissue induces OA progress,and the inflammation factors play a significant role in OA progress.UC-MSCs could protect cartilage and synovial membrane of joints and inhibit the inflammatory response.Therefore,this study provides new therapy method for OA.