Objective:To observe the effects of allogeneic compact bone derived-mesenchymal stem cells ( CB-MSCs) on pro-liferation and differentiation of T cells,and investigate the molecular mechanisms of the immunosuppressive ability.Methods:With an established co-culture system of CB-MSCs and mouse spleen lymphocytes ( SP) in vitro,we observed the effects of CB-MSCs on prolif-eration,apoptosis and cell cycle of SP by MTS/PES assay and flow cytometry.Also,we measured the effects of CB-MSCs on regulatory T cells ( Treg) ratio and expressions of CCR5,CCR7 and CXCR3 in SP.Results:CB-MSCs could obviously inhibit the PHA-stimulated SP proliferation with a dose-dependent manner;MSCs could significantly inhibit the spontaneous apoptosis of SP and induce SP cell cycle G0/G1 phase arrest.After co-culture with SP,CB-MSCs could obviously increase the proportion of Treg in SP,down-regulate the expression of CXCR3 and CCR5,as well as up-regulate the expression of CCR7.Conclusion: Allogeneic CB-MSCs can significantly inhibit cell proliferation of SP,the mechanisms mainly involved the G0/G1 cell cycle arrest rather than apoptosis induction.In addition, CB-MSCs can exert immunomodulatory effects by increasing the Treg ratio,regulating the expressions of chemokine receptors.

Plasma cell leukemia (PCL) is a plasma cell proliferative disorder with strong invasiveness, rapid progression and poor prognosis. The incidence of PCL is about (0.04-0.05)/100 000 per year. According to the multiple myeloma (MM) history, PCL can be divided into primary plasma cell leukemia (PPCL) and secondary plasma cell leukemia (SPCL). PPCL accounts for about 60% of PCL, and it is in the stage of leukemia at diagnosis and has no history of MM. SPCL accounts for the remaining 40% of PCL, and mostly shows as the MM end-stage manifestation, but also can be secondary to Waldenstrom macroglobulinemia, B-cell lymphoma, chronic lymphoblastic leukemia, amyloidosis, etc. Patients who progress from MM to SPCL account for 2%-4% of all MM patients. Due to the low incidence and strong clinical heterogeneity of PCL, the evidence-based medicine about PCL is relatively lacking, this article reviews the clinical characteristics of PCL and progress in its diagnosis and treatment.

BACKGROUNDRadiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences, and currently no effective therapy exists. This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI), and to explore the potential immunoprotective role of MSCs.

METHODSBALB/c mice were treated with 8 Gy TBI, and then some were administered CB-MSCs isolated from C57BL/6 mice. Survival rates and body weight were analyzed for 14 days post-irradiation. At three days post-irradiation, we evaluated IFN-γ and IL-4 concentrations; CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) percentage; CXCR3, CCR5, and CCR7 expressions on CD3(+) T cells; and splenocyte T-bet and GATA-3 mRNA levels. CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.

RESULTSAfter lethal TBI, compared to non-transplanted mice, CB-MSC-transplanted mice exhibited significantly increased survival, body weight, and CFU-GM counts of bone marrow cells (P < 0.05), as well as higher Treg percentages, reduced IFN-γ, CXCR3 and CCR5 down-regulation, and CCR7 up-regulation. CB-MSC transplantation suppressed Th1 immunity. Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells, and CB-MSC co-culture reversed this inhibition.

CONCLUSIONAllogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity, and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition, expanding Tregs, regulating T cell chemokine receptor expressions, and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

Animals ; Bone and Bones ; cytology ; Cytokines ; metabolism ; Female ; Granulocyte-Macrophage Progenitor Cells ; cytology ; Male ; Mesenchymal Stem Cell Transplantation ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Whole-Body Irradiation ; adverse effects