Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs.

Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3.

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents, such as vitamin D compounds, is a potential regimen to treat acute myeloid leukemia (AML) patients who are unfit for high-intensity chemotherapy. The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3 (1,25-D3). Here, firstly, cBioPortal database was used and we found out that vitamin D receptor (VDR) was highly expressed in acute monocytic leukemia (M5) and high VDR expression was associated with a poor survival of AML patients.

BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro.

The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood. Recently, we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants. Here, we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs).

Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma under chemotherapy.

Accumulating evidences have shown that adipokines secreted from adipocytes contributes to tumor development, especially leptin. However, underlying mechanisms remain unclear. This study aims to explore the effect of leptin on development and chemoresistance in multiple myeloma cells and the potential mechanism.

Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6.

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected.

Microvesicles secreted from human multiple myeloma cells promote angiogenesis.

Aim: To investigate whether human multiple myeloma (MM) cells secrete microvesicles (MVs) and whether the MVs secreted from MM cells (MM-MVs) promote angiogenesis.

Methods: RPMI8226 human MM cells and EA.hy926 human umbilical vein cells were used.

Serum deprivation elevates the levels of microvesicles with different size distributions and selectively enriched proteins in human myeloma cells in vitro.

Aim: To investigate the effects of serum deprivation (SD) on microvesicles (MVs) secreted from human myeloma cells and the implications for disease progression.

Methods: RPMI 8226, U266, and KM3 human myeloma cells were incubated in medium containing 10% (non-SD) or 1% fetal bovine serum (SD) and MVs were isolated. The levels and size distribution of MVs were analyzed with flow cytometry.

Immune protection function of multipotent mesenchymal stromal cells: role of transforming growth factor-β1.

The immunosuppressive functions of multipotent mesenchymal stromal cells (MSCs) may give cancer cells a survival advantage. This study tests the hypothesis that MSCs protect leukemia cells from immune clearance. Our results demonstrate that MSCs are capable of inhibiting peripheral blood mononuclear cells (PBMNCs) proliferation and their migration toward leukemic cells by the reduction of CCL5 and CXCL12.

[siRNA-induced down-regulation of Livin expression increases spontaneous apoptosis in K562 cell line].

This study was aimed to observe the effects of siRNA on Livin expression and function in K562 cells. Livin siRNA were designed and synthesized, then were transfected into K562 cells by using AMAXA nucle transfactor. Expressions of Livin mRNA and protein in transfected K562 cells was detected by RT-PCR and Western blot respectively.

Functional characteristics of mesenchymal stem cells derived from bone marrow of patients with myelodysplastic syndromes.

Mesenchymal stem cells (MSCs) have emerged as excellent candidates for clinical application because of their capabilities of immunomodulatory and supporting hematopoiesis. Nevertheless, it is unclear whether the characteristics of MSCs are altered in diseased states. In this study, we obtained and expanded MSCs from bone marrow of patients with myelodysplastic syndromes (MDS).

The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia.

Dendritic cells (DCs) are specialised antigen-presenting cells that play crucial roles in the initiation and regulation of immune responses. Recently, mesenchymal stem cells (MSCs) have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even DCs. However, the mechanisms underlying these immunoregulatory effects of MSCs induced DCs are poorly understood.

Immunomodulatory function of regulatory dendritic cells induced by mesenchymal stem cells.

Mesenchymal stem cells (MSCs) provide an excellent model for development of stem cell therapeutics, and their potential treatment in the immunopathogenic diseases have gained further interest after demonstration of immunomodulatory effects on complicated interactions between T cells and even dendritic cells (DCs). However, the mechanisms underlying these immunoregulatory effects of MSCs are poorly understood. In this study, we show that bone marrow derived MSCs can differentiate mature DCs (mDCs) into a distinct regulatory DC population.

Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients.

Aim: To investigate the pharmacokinetics of imatinib in Chinese chronic myelogenous leukemia (CML) patients.

Methods: Fourty-six naïve Chinese CML patients treated with imatinib (400 and 600 mg daily, n=36 and 10, respectively) were recruited. The correlations of imatinib (400 mg) trough plasma concentrations (C(mins)) with the patients' characteristics and responses were analyzed.

A comparative study of outcomes of idarubicin- and etoposide-intensified conditioning regimens for allogeneic peripheral blood stem cell transplantation in patients with high-risk acute leukemia.

Aim: To analyze the results of idarubicin (IDA)- versus etoposide (VP16)-intensified myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-SCT) for high-risk acute leukemia.

Methods: From January 2005 to June 2008, 48 consecutive patients (male: n=29; median age: 30 years, range 14-51 years) with high-risk acute leukemia underwent allo-SCT following an IDA- or VP16-intensified conditioning regimen. The conditioning regimens were modified BUCY2 (busulfan+cyclophosphamide) consisting of IDA (15 mg/m2 per day, days -12 to -10) or VP16 (25 mg/kg per day, days -3 to -2) and CY/TBI (cyclophosphamide/total body irradiation) intensified with IDA (15 mg/m2 per day, days -6 to -5) or VP16 (25 mg/kg per day, days -3 to -2) for acute myeloid leukemia and acute lymphoblastic leukemia, respectively.

Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation.

Background: Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after allo-HSCT.

Methods: Seven patients, median age 34 years, with relapse of acute leukaemia after allo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days.

[A clinical study of treating 120 cases of adult chronic myelocytic leukemia with imatinib mesylate].

Objective: To analyze and evaluate the clinical efficacy and safety of imatinib mesylate (IM) as a tyrosine kinase inhibitor on Ph-positive or BCR/ABL positive chronic myelogenous leukemia (CML).

Methods: 120 patients diagnosed as CML with positive Ph chromosome were treated with IM 400 mg/d for CML in chronic phase (CP) (n = 90) or 600 mg/d for CML in accelerated or blastic phase (AP or BP) (n = 30) once daily. Hematological, cytogenetic and molecular effects of IM on the disease process of these patients were evaluated with blood and marrow cells morphology examination, G-band conventional cytogenetics analysis for Ph chromosome and PCR assay for BCR/ABL gene.

[Inhibitory Effect of EGCG on angiogenesis induced by multiple myeloma cell line KM3 and its mechanism].

The aim of this study was to investigate the effect of [(-)-epigallocatechin-3-gallate (EGCG)] on angiogenesis induced by multiple myeloma cell line KM3 and its mechanism. The effects of KM3 cell supernatant after being treated with EGCG in different concentrations on migration and vascular formation ability of endothelial cell line HUVEC were investigated through culture of MM cell line KM3 in vitro. The secretion level of vascular endothelial growth factor (VEGF) in KM3 cell supernatant and the expression level of VEGF mRNA in KM3 were detected by ELISA and RT-PCR respectively.

Phenotypic and functional comparison of mesenchymal stem cells derived from the bone marrow of normal adults and patients with hematologic malignant diseases.

Mesenchymal stem cells (MSCs) have received much attention for their ability to differentiate into various cell types under specific conditions and to support the proliferation of hematopoietic stem cells. However, it is unclear whether the characteristics of MSCs are altered in different disease states. In this study, we obtained and expanded MSCs from bone marrow of patients with acute lymphoblastic leukemia (ALL), Hodgkin disease (HD), and non-Hodgkin lymphoma (NHL).

Small interfering RNA of cyclooxygenase-2 induces growth inhibition and apoptosis independently of Bcl-2 in human myeloma RPMI8226 cells.

Aim: To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro.

Methods: Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Western blot analysis, respectively. The COX-2 siRNA fragment targeting exon 5 of COX-2 gene was transfected into the cells with the Amaxa nucleofection technique.

[Role of amifostine against the effect of etoposide on non-Hodgkin lymphoma bone marrow derived mesenchymal stem cells: an in vitro experiment].

Objective: To study the protective role of amifostine (WR-2721) in the mesenchymal stem cells (MSC) derived from non-Hodgkin lymphoma (NHL) bone marrow treated with etoposide (VP-16).

Methods: MSC were obtained from non-Hodgkin lymphoma bone marrow, cultured in expanded medium, and then divided into 4 groups: Group A, without treatment by either WR-2721 or VP-16 and used as control group, Group B, treated with WR-2721, Group C, treated with WR-2721 + VP-16, and Group D, treated with VP-16 alone. Inverted microscopy was used to observe the growth of the MSC.

[Proliferation inhibiting and apoptosis inducing effects of parthenolide on human multiple myeloma cells].

Objective: To investigate the effect of parthenolide (PTL) on human multiple myeloma (MM) cells in vitro and its mechanism.

Methods: Human MM cells of the line PRMI8266 were cultured and treated with PTL of the concentrations of 1, 2.5, 5, 7.