Study On Mechanism of Bone Marrow Mesenchymal Stem Cell in Treating Patients with Rheumatoid Arthritis.

To explore mechanism of Mesenchymal stem cells in treating Rheumatoid arthritis.

(1) MSCs were isolated from Bone marrow samples of Rheumatoid arthritis(RA)patients and purified by density gradient centrifagation and cultured in vitro. Morphology, immunophenotype, and proliferative property of bMSC and colony forming unit-fibroblast (CFU-F) were measured and analyzed. (2) In an in vitro co-culture system, MSCs were observed to modulate proliferation,activation, and maturation of T and B lymphocytes of Rheumatoid arthritis(RA)patients. The expression of IL-1?ATNF-a?ATGF-β were obviously changed.(3) Bone marrow- derived BMSCs of wistar rats were isolated and cultured in vitro routinely and the fourth passage as taken for identification of specific surface antigens by flowcytometry, then were labled with 5- BrdU in vitro. The model of collagen-induced arthritis (CIA) rats were established. 5- BrdU labled BMSCs were implanted through tail vein to model rats. At 4 weeks after BMSCs transplantation, immunohistochemical examinations were used to investigate BMSCs aggregate around the knee joints.and identify the contribution of bone marrow– derived cells to joints damage repair.

(1) The culture expanded cells from RA patients presented a typical fibroblast-like morphology. Cells were positive for SH2(CD105),CD71,and CD44, but negative for CD45.Their proliferative capacity and CFU-F number were similar to those of bMSCs from healthy donors. (2) MSCs significantly inhibited T,B cell proliferation. MSCs also could down-regulating the levels of IL-1, TNF and up-regulating TGF-β. (3) Flow cytometry showed that BMSCs expressed CD44, CD71and CD105, but no CD45,CD34. At 4 weeks after the cells transplantation, the implanted cells were detected in the damaged joints of the model rats, which is not founded in normal knee joints of the rats'.and at same time there are more OPG(osteoprotegerin) positive.

(1) In the aspect of morphology, immuno -phenotypen, proliferative property and colony forming unit-fibroblast (CFU-F),MSCs from bone marrow of RA patients are not different from those of MSCs isolated from bone marrow of normal donors,MSCs from the bone marrow of RA patients have the potentiality in clinical application.(2) Human bone marrow MSCs inhibited Tcell and Bcell activation and proliferation in patients with RA in vitro. And these immuno –modulatory effects were not MHC-restricted. (3) bone marrow mesenchymal stem cells prevents tissue damage in arthritis. Allogeneic MSCs can engraft at sites of tissue damage,and prepair damage. That provided positive results for developing effective therapy for Rheumatoid arthritis.

No relevant conflicts of interest to declare.