Flk-1~+ bone marrow mesenchymal stem cell transplantation upregulates interleukin-6 level: Whether it simultaneously aggravates collagen-induced arthritis in mice? / 中国组织工程研究

ABSTRACT

BACKGROUND: Immunoloregulation of mesenchymal stem cells (MSCs) is commonly approved. Previous studies have confirmed the ability of Flk-1~+ bone marrow MSCs (BMSCs) to inhibit T/B lymphocyte proliferation in vitro. OBJECTIVE: To investigate the therapeutic effect of Flk-1~+ BMSCs in collagen-induced arthritis mice.METHODS: A total of 18 healthy male DBA-1(H-2K~q) mice aged 10 weeks were randomly divided into 3 groups. All the mice were injected at the base of the tail with bovine type II collagen (CII), and received a booster injection of CII on day 21 to establish the CIA mice model. DBA-1(H-2K~q)mouse Flk-1~+ BMSCs were isolated in vitro by the density gradient centrifugation and adherence screening. Following initial immunity, mice in the cell transplantation group were infused with Flk-1~+ BMSCs (1-2)×106 cells/mouse via the caudal vein. Mice in the cell transplantation group were injected with the same volume of Flk-1~+ BMSCs during booster. Mice in the model control group were injected with an equal volume of saline 0 or 21 days following initial immunity. Following initial immunity and booster immunization, claw pad thickening and clinical score were observed, changes of joint pathology and dynamic changes in serum factor mass concentration were determined in mice. RESULTS AND CONCLUSION: Compared with the model control group, no significant difference in claw pad thickening and mean clinical score was detected in the cell transplantation group following initial immunity (P > 0.05), with the presence of obvious damage to synovial membrane and inflammatory cell infiltration. Mass concentration of each serum cell factor was similar. The claw pad was significantly thickened (P < 0.01), mean clinical score reached 3.35 points, with severe damage to synovial membrane, proliferation of blood capillary in the cell transplantation group following booster immunization. Interleukin-6 levels were greatly increased at day 28 following initial immunity (P < 0.1), but decreased at day 35 following initial immunity (P < 0.1). Results indicated that in the collagen-induced arthritis mouse models, Flk-1~+ BMSC transplantation did not obtain prospective therapeutic efficacy, but aggravation of arthritis was observed in the cell transplantation group following booster immunization. Upregulation of interleukin-6 concentration could aggravate the behavior symptom of rheumatoid arthritis mice.