Experimental study on the treatment of knee osteoarthritis based on oxidized graphene granule lubricant and umbilical cord mesenchymal stem cells / 国际生物医学工程杂志

ABSTRACT

Objective:To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) loaded by graphene oxide (GO) on cartilage repair in two KOA animal models.Methods:30 male New Zealand rabbits aged 12 weeks were randomly divided into A group ( n=15) and B group ( n=15). In the A group, the KOA model was established by the improved Hulth and cartilage defect method, and in the B group, the KOA model was established by the modified papain controlled-release injection method. After the modeling, the rabbits model in each group were divided into 4 subgroups, including blank control group ( n=3), GO group ( n=4), UCMSCs group ( n=4) and GO+UCMSCs group ( n=4). In these subgroups, the rabbit models were respectively treated injected with 0.5 ml of NaCl solution with 9 g/L, GO granular lubricant (GO with 30 μg/ml and solvent with hyaluronic acid with 0.25%), UCMSCs suspension (5×10 6 /ml), and mixed suspension of UCMSCs loaded by GO (GO with 30 μg/ml and UCMSCs with 5×10 6/ml) in right knee joint cavity. The serum levels of NO, collagen type Ⅱ(COL-Ⅱ), glycosaminoglycan (GAG), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). Results:Eight weeks after the treatment, the serum levels of NO, IL-6 and TNF-α in GO+UCMSCs group were lower than those of the blank control group (all P<0.01), and the serum levels of COL-Ⅱ and GAG in GO+UCMSCs group were higher than those of the blank control group (all P<0.01). The serum NO level of the blank control group in group A was lower than that of the blank control group in group B [(22.097±0.352) ng/ml vs (23.662±0.056) ng/ml, P<0.05]. The serum COL-Ⅱ levels of the UCMSCs group and GO+UCMSCs group in group A were higher than those of group B respectively [(15.589±0.063) ng/ml vs (14.429±0.092) ng/ml, and (19.372±0.063) ng/ml vs (16.257±0.416) ng/ml, all P<0.01]. The serum GAG levels of the blank control group and the GO+UCMSCs group in group A were higher than those in group B respectively [(23.832±0.891) ng/ml vs (18.709±0.552) ng/ml, and (37.439±2.155) ng/ml vs (26.554±0.450) ng/ml, all P<0.01). The serum IL-6 levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(16.082±0.323) ng/ml vs (18.367±0.861) ng/ml, P<0.05; (7.426±0.294) ng/ml vs (8.680±0.242) ng/ml, P<0.01]. The serum TNF-α levels of the blank control group and the GO+UCMSCs group in group A were lower than those in group B respectively [(9.466±0.177) ng/ml vs (10.013±0.197) ng/ml, P<0.05; (5.139±0.183) ng/ml vs (6.210±0.058) ng/ml, P<0.01]. Conclusions:GO loaded UCMSCs can promote the secretion of chondrocytes in rabbit KOA models, reduce inflammatory levels in joints, and play a role in cartilage repair.