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Chen Tian, Guoguang Zheng, Hongqing Zhuang, Xubin Li, Dongzhi Hu, Lei Zhu, Wang Tengteng, M James You, Yizhuo Zhang
Acute myeloid leukemia (AML) is not sensitive to chemotherapy partially because of the protection of AML cells by mesenchymal stromal cells (MSCs). Our previous studies found that MSCs protected AML cells from apoptosis through the c-Myc-dependent pathway. However, the mechanism by which MSCs regulate c-Myc in AML cells is still unknown. To elucidate the mechanism, we performed microRNA array analysis of AML cell lines and validated by TaqMan realtime PCR. The results showed that the expression of microRNA-494 (miR-494) in AML cells after coculture with MSCs was down-regulated...
October 3, 2016: Journal of Cellular Physiology
Guo-Zheng Pan, Feng-Xian Zhai, Yin Lu, Zhi-Gang Fang, Rui-Fang Fan, Xiang-Fu Liu, Dong-Jun Lin
The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells...
October 2016: Oncology Reports
Martin Sebastian Staege
Gene Expression Music Algorithm (GEMusicA) is a method for the transformation of DNA microarray data into melodies that can be used for the characterization of differentially expressed genes. Using this method we compared gene expression profiles from endothelial cells (EC), hematopoietic stem cells, neuronal stem cells, embryonic stem cells (ESC), and mesenchymal stem cells (MSC) and defined a set of genes that can discriminate between the different stem cell types. We analyzed the behavior of public microarray data sets from Ewing sarcoma ("Ewing family tumors," EFT) cell lines and biopsies in GEMusicA after prefiltering DNA microarray data for the probe sets from the stem cell signature...
2016: Stem Cells International
Cesarina Giallongo, Alessandra Romano, Nunziatina Laura Parrinello, Piera La Cava, Maria Violetta Brundo, Vincenzo Bramanti, Fabio Stagno, Paolo Vigneri, Annalisa Chiarenza, Giuseppe Alberto Palumbo, Daniele Tibullo, Francesco Di Raimondo
It is well known that mesenchymal stem cells (MSC) have a role in promotion of tumor growth, survival and drug-resistance in chronic myeloid leukemia (CML). Recent reports indicated that a subpopulation of myeloid cells, defined as granulocyte-like myeloid-derived suppressor cells (G-MDSC) is increased in these patients. So far, the role of MSC in MDSC expansion and activation into the BM microenvironment remains unexplored. To address this question, here we use a specific experimental model in vitro, co-culturing MSC with peripheral blood mononucleated cells (PBMC) from normal individuals, in order to generate MSC-educated G-MDSC...
2016: PloS One
Tsung Chi Lu, Guan-Hao Zhao, Yao Yun Chen, Chia-Ying Chien, Chi-Hung Huang, Kwang Hui Lin, Shen Liang Chen
Tumor suppressor protein p53 plays important roles in initiating cell cycle arrest and promoting tumor cell apoptosis. Previous studies have shown that p53 is either mutated or defective in approximately 50% of human cancers; therefore restoring normal p53 activity in cancer cells might be an effective anticancer therapeutic approach. Herein, we designed a chimeric p53 protein flanked with the MyoD N-terminal transcriptional activation domain (amino acids 1-62, called M3) and a poly-arginine (R12) cell penetrating signal in its N-and C-termini respectively...
2016: Journal of Cancer
Ni Zhu, Huafang Wang, Jieping Wei, Binsheng Wang, Wei Shan, Xiaoyu Lai, Yanmin Zhao, Jian Yu, He Huang
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are pivotal components of the leukemic microenvironment. BM-MSCs have been previously reported to promote the proliferation of leukemic cells. To further understand the molecular mechanisms of BM-MSC-induced proliferation of leukemic cells, the present study co-cultured acute lymphoblastic leukemia (ALL) Reh cells with BM-MSCs. The current study used methods including shRNA, flow cytometry, MTT, reverse transcription-quantitative polymerase chain reaction, ELISA and western blotting...
August 2016: Molecular Medicine Reports
Taghrid Mohamed Gaafar, Inas Ismail Raafat, Azza Ahmed Aly, Nagwa Abd El-Ghaffar Mohamed, Reem Jan Farid, Neveen Ezzat Saad, Rabab El-Hawary, Naglaa Mostafaa, Mirhan Mohamed Ahmed
BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at the cytogenetic level by Philadelphia (ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into several mesenchymal tissues. AIM: To observe the biological characteristics of MSCS from CML patients and to determine whether MSCs harbor the abnormal BCR/ABL translocation similar to CML bone marrow cells...
June 15, 2015: Open Access Macedonian Journal of Medical Sciences
Xiaoyan Zhang, Huaijun Tu, Yazhi Yang, Qian Wan, Lijun Fang, Qiong Wu, Jian Li
Chronic myeloid leukemia (CML) is a three-stage myeloproliferative disease caused by translocation between chromosomes 9 and 22. Although tyrosine kinase inhibitors (TKI) are highly effective in the treatment of CML, numerous clinical trials have shown that many patients become refractory or drug resistance, especially those in the blastic crisis of CML. The molecular mechanisms underlying CML, however, remain poorly understood. In the present study, we used a coculture model to address possible mechanisms underlying the involvement of bone marrow microenvironment in the drug resistance of CML...
September 2016: International Journal of Hematology
Fang Chen, Feng-xia Ma, Yang Li, Fang-yun Xu, Ying Chi, Shi-hong Lu, Zhong-chao Han
OBJECTIVE: To investigate the effect of human umbilical cord-derived mesenchymal stem cells (UC-MSC) on the differentiation of leukemic cells. METHODS: The co-culture system of UC-MSC with acute promyelocytic leukemic cell line NB4 cells was constructed in vitro,and the differentiation status of the leukemic cells was assessed by cell morphology,nitroblue tetrazolium reduction test,and cell surface differentiation marker CD11b. RESULTS: UC-MSC induced the granulocytic differentiation of NB4 cells...
April 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
I Tzoran, A Rebibo-Sabbah, B Brenner, A Aharon
INTRODUCTION: Acute myeloid leukemia (AML) is characterized by rapid growth of leukemic blast cells. Extracellular vesicles (EVs) are shed from normal and pathologic cells and express membrane proteins and antigens, reflecting their cellular origin. AIM: To explore whether bone marrow EVs of AML patients originate from blast cells and are capable of influencing hematopoietic stem cells (HSC) in a pseudo-natural microenvironment obtained by co-culture of HSC with mesenchymal stem cells (MSC)...
April 2016: Thrombosis Research
S Wen, M Dooner, Y Cheng, E Papa, M Del Tatto, M Pereira, Y Deng, L Goldberg, J Aliotta, D Chatterjee, C Stewart, A Carpanetto, F Collino, S Bruno, G Camussi, P Quesenberry
Mesenchymal stromal cells (MSC) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 h to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 h post-irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500 cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow...
May 6, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Belén Blanco, M Carmen Herrero-Sánchez, Concepción Rodríguez-Serrano, María Lourdes García-Martínez, Juan F Blanco, Sandra Muntión, Mariano García-Arranz, Fermín Sánchez-Guijo, Consuelo Del Cañizo
INTRODUCTION: The ability of mesenchymal stromal cells (MSC) to suppress T-cell function has prompted their therapeutic use for graft-versus-host disease (GVHD) control. However, as MSC also modulate the activity of NK cells, which play an important role in graft-versus-leukemia (GVL) reaction, their administration could hamper this beneficial effect of allogeneic hematopoietic stem cell transplantation. MSC can be expanded from several sources, especially bone marrow and fat, but it is not well established if the cell source makes a difference in their immunoregulatory capacity...
April 27, 2016: European Journal of Haematology
D Pal, H J Blair, A Elder, K Dormon, K J Rennie, D J L Coleman, J Weiland, K S Rankin, A Filby, O Heidenreich, J Vormoor
Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction...
August 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Yungjun Tang, Qing Guo, Yaqin Zhi, Xin Jin, Bing Xia, Shanqi Guo, Chen Tian, Yizhuo Zhang
OBJECTIVE: To explore the role of CXCR4/STAT3 in mesenchymal stromal cell (MSC)-mediated drug resistance of AML cells. METHODS: AML cell lines U937 and KG1a and primary AML cells were co-cultured with MSC from bone marrow of healthy donors. The AML cell lines cultured alone were used as control. Apoptosis induced by mitoxantrone was measured by flow cytometry. Expression of CXCR4 and STAT3 protein were detected by Western blot. After incubated with STAT3 inhibitor Cucurbitacin I or CXCR4 antagonist AMD3100, the apoptosis of AML cells induced by mitoxantrone was evaluated...
February 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Anna Lange-Consiglio, Alessio Romaldini, Alessio Correani, Bruna Corradetti, Paola Esposti, Maria Francesca Cannatà, Claudia Perrini, Maria Giovanna Marini, Davide Bizzaro, Fausto Cremonesi
Recent studies have revealed the presence of a mesenchymal stem cell (MSC) population in human and in gilt granulosa cells (GCs), thus increasing the interest in identifying the same population in the bovine species. We first isolated GCs by scraping from bovine preovulatory follicles and then tested several different media to define the ideal conditions to select granulosa-derived stem cells. Although expressing MSC-associated markers, none of the media tested proven to be efficient in selecting MSC-like cells that were able to differentiate into mesodermic or ectodermic lineages...
April 2016: Cellular Reprogramming
Bing Z Carter, Po Yee Mak, Ye Chen, Duncan H Mak, Hong Mu, Rodrigo Jacamo, Vivian Ruvolo, Stefan T Arold, John E Ladbury, Jared K Burks, Steven Kornblau, Michael Andreeff
To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB...
April 12, 2016: Oncotarget
Wen-Long Hu, Ping-Ping Wu, Chang-Chang Yin, Jian-Ming Shi, Ming Yin
OBJECTIVE: To study the effects of LIF combined with bFGF on the proliferation, stemness and senescence of hUC-MSC. METHODS: Experiments were divided into 4 groups: control group, in which the cells were treated with complete medium (α-MEM containing 10% FBS); group LIF, in which the cells were treated with complete medium containing 10 ng/ml LIF; group bFGF, in which the cells were treated with complete medium containing 10 ng/ml bFGF; combination group, in which the cells were treated with complete medium containing 10 ng/ml LIF and 10 ng/ml bFGF...
February 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
L Zanotti, R Angioni, B Calì, C Soldani, C Ploia, F Moalli, M Gargesha, G D'Amico, S Elliman, G Tedeschi, E Maffioli, A Negri, S Zacchigna, A Sarukhan, J V Stein, A Viola
Mesenchymal stem cells (MSC) represent a promising therapeutic approach in many diseases in view of their potent immunomodulatory properties, which are only partially understood. Here, we show that the endothelium is a specific and key target of MSC during immunity and inflammation. In mice, MSC inhibit activation and proliferation of endothelial cells in remote inflamed lymph nodes (LNs), affect elongation and arborization of high endothelial venules (HEVs) and inhibit T-cell homing. The proteomic analysis of the MSC secretome identified the tissue inhibitor of metalloproteinase-1 (TIMP-1) as a potential effector molecule responsible for the anti-angiogenic properties of MSC...
May 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Kui Song, Weichao Li, Min Li
Acute myeloid leukemia (AML) is an extremely rare complication that can be observed following mesenchymal stem cells (MSC) transplantation for traumatic brain injury (TBI). Few cases have been reported thus far. The present study reports a case of acute promyelocytic leukemia (APL) following MSC transplantation in a 36-year-old female. The patient presented with a fever and dermatorrhagia with an associative abnormal coagulation test almost 2 months after the MSC transplantation for TBI. The routine blood test, bone marrow (BM) test, and examination of the promyelocytic leukemia/retinoic acid receptor-α and mixed lineage leukemia chimeric genes confirmed the diagnosis of APL and disseminated intravascular coagulation (DIC)...
November 2015: Oncology Letters
S Geyh, M Rodríguez-Paredes, P Jäger, C Khandanpour, R-P Cadeddu, J Gutekunst, C M Wilk, R Fenk, C Zilkens, D Hermsen, U Germing, G Kobbe, F Lyko, R Haas, T Schroeder
Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development...
March 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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