Study On Mechanism Of Bone Marrow Mesenchymal Stem Cell In Treating Patients With Rheumatoid Arthritis

Rheumatoid arthritis(RA) is a whole-body self-immunological disease.Its remarkable symptom is articulation's pain with deformity and function damaged severely.At present,It's still difficult to find a effective method to control and cure this disease.Mesenchymal stem cells(MSCs) are multipotential nonhematopoietic progenitor cells capable of differentiating into multiple lineages of the mesenchyme.MSCs have emerged as a promising therapeutic modality for tissue regeneration and repair.Further clinical interest has been raised by the observation that MSCs are immunoprivileged and,more importantly,display immunomodulatory.A better understanding of Mesenchymal stem cells will benefit for realizing a novei therapeutic strategy to modulate immune responses in a variety of immune-mediated diseases,this study aim at the mechanism of Mesenchymal stem cells in treating Rheumatoid arthritis.In the first part of this study,we investigated the biological characteristics of mesenchymal stem cells(MSCs) from patients with Rheumatoid arthritis(RA),MSCs from bone marrow samples of Rheumatoid arthritis(RA) patients were isolated,cultured and expanded.Morphology,immunophenotype,and proliferative property of MSC and colony forming unit-fibroblast(CFU-F) were measured and analyzed.The result indicate that 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 MSCs from healthy donors,the biological characteristics of MSC from bone marrow of RA patients are not different from those of MSC isolated from bone marrow of normal donors,MSCs from the bone marrow of RA patients have the potentiality in clinical applicationl..At same time,In an in vitro co-culture system,MSCs were observed to modulate proliferation,activation,and maturation of T and B lymphocytes.The expression of IL-1,TNF-a,TGF—βwere obviously changed. MSCs also could down-regulating the levels of IL-1,TNF and up-regulating TGF-β.And these immuno -modulatory effects were not MHC-restricted.In the second part primarily presented MSCs' immunomdulation on rats with Rheumatoid arthritis.Local as well as systemic infusion of MSCs systemically uppressed the host immune response.And 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.The third part mainly investigated one patients with Rheumatoid arthritis.Who had received treatment with allogeneic MSCs which isolated from Umbilical cord blood(UCB). We observed safety and efficacy using MSCs in clinical.When MSCs were infused without any infusion-related adverse events.After treatment with MSCs,the pain alleviated,with the result of ESR,RF and Tc test recovered gradually.