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Peter Bader, Zyrafete Kuçi, Shahrzad Bakhtiar, Oliver Basu, Gesine Bug, Michael Dennis, Johann Greil, Aniko Barta, Krisztián M Kállay, Peter Lang, Giovanna Lucchini, Raj Pol, Ansgar Schulz, Karl-Walter Sykora, Irene von Luettichau, Grit Herter-Sprie, Mohammad Ashab Uddin, Phil Jenkin, Abdulrahman Alsultan, Jochen Buechner, Jerry Stein, Agnes Kelemen, Andrea Jarisch, Jan Soerensen, Emilia Salzmann-Manrique, Martin Hutter, Richard Schäfer, Erhard Seifried, Thomas Klingebiel, Halvard Bonig, Selim Kuçi
The inability to generate mesenchymal stromal cells (MSCs) of consistent potency likely is responsible for inconsistent clinical outcomes of patients with aGvHD receiving MSC products. We developed a novel MSC manufacturing protocol characterized by high in vitro potency and near-identity of individual doses, referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of the 69 patients who have received MSC-FFM. These were 51 children and 18 adults with refractory aGvHD grade II (4%), III (36%) or IV (59%)...
January 29, 2018: Bone Marrow Transplantation
Jian Xu, Xue Li, Allison Cole, Zachary Sherman, Wei Du
Hematopoietic stem cells preserve their ability to self-renew and differentiate to different lineages in the bone marrow (BM) niche, which is composed in large part by BM stromal cells. Studies have shown that altered signaling in the BM niche results in leukemia initiation or progression. Fanconi anemia (FA) is an inherited BM failure syndrome associated with extremely high risk of leukemic transformation. By using two FA mouse models, here we have investigated the hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs)...
January 27, 2018: Stem Cells
Jiancheng Wang, Xin Liu, Yuan Qiu, Yue Shi, Jianye Cai, Boyan Wang, Xiaoyue Wei, Qiong Ke, Xin Sui, Yi Wang, Yinong Huang, Hongyu Li, Tao Wang, Ren Lin, Qifa Liu, Andy Peng Xiang
BACKGROUND: Despite the high cure rate of T cell acute lymphoblastic leukemia (T-ALL), drug resistance to chemotherapy remains a significant clinical problem. Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from chemotherapy, but the underlying mechanisms are poorly understood. In this study, we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells, thus providing a promising clinical therapy target. METHODS: Cell viability was determined using the viability assay kit CCK-8...
January 22, 2018: Journal of Hematology & Oncology
Chinnapaka Somaiah, Atul Kumar, Renu Sharma, Amit Sharma, Trishna Anand, Jina Bhattacharyya, Damodar Das, Sewali Deka Talukdar, Bithiah Grace Jaganathan
BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine...
January 19, 2018: Journal of Biomedical Science
Lilian Grigorian-Shamagian, Soraya Fereydooni, Weixin Liu, Antonio Echavez, Eduardo Marbán
The heart is known for its resistance to cancer. Although different conjectures have been proposed to explain this phenomenon, none has been tested. We propose that the heart microenvironment may exert anti-cancer properties. So, our objective was to test the anti-oncogenic potential of cardiac-derived extracellular vesicles (EVs). For that EVs secreted by cardiosphere-derived cells (CDCs, heart progenitor cells) were tested in vitro on fibrosarcoma HT1080. In vivo models comprised the xenograft HT1080 fibrosarcoma in athymic mice (n=35), and spontaneous acute lymphocyte leukemia in old rats (n=44)...
November 21, 2017: Oncotarget
Jing Huang, Zhi Liu, Yufan Sun, Qi Zhong, Li Xu, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu
The present study aimed to characterize the epigenetic architecture by studying the DNA methylation signature in bone marrow mesenchymal stem cells (BM‑MSCs) from patients with acute myeloid leukemia (AML). Microarray dataset GSE79695 was downloaded from the Gene Expression Omnibus database. Differentially methylated sites and differentially methylated CpG islands were identified in BM‑MSC samples from patients with AML compared with controls. MicroRNAs (miRs) encoding genes covering differentially methylated sites were found and the regulation network was constructed...
February 2018: International Journal of Molecular Medicine
Roland Christian Schelker, Sabine Iberl, Gunnar Müller, Christina Hart, Wolfgang Herr, Jochen Grassinger
OBJECTIVES: Multipotent mesenchymal stromal cells (MSCs) play a central role within the bone marrow (BM) niche, supporting hematopoiesis via soluble factors like cytokines and chemokines. In our study, we sought to investigate the effect of blocking transforming growth factor beta 1 (TGF-β1) and C-X-C motif chemokine 12 (CXCL12) receptor CXCR4 on acute myeloid leukemia (AML) cells in an MSC co-culture system. METHODS: Human MSCs were obtained by BM aspirates and their phenotype and functional properties were confirmed in vitro...
November 15, 2017: Hematology (Amsterdam, Netherlands)
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Zhiqiang Wang, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Teresa McQueen, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
October 13, 2017: Oncotarget
Hakan Ozdogan, Bala Gur Dedeoglu, Yasemin Oztemur Islakoglu, Alp Aydos, Sevil Kose, Arzu Atalay, Zeynep Arzu Yegin, Ferit Avcu, Duygu Uckan Cetinkaya, Osman Ilhan
Multipotent mesenchymal stem cells (MSC) are key components of the bone marrow (BM) microenvironment. The contribution of this microenvironment to the pathophysiology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is not well defined. A recent study in mice demonstrated that DICER1 gene deletion in osteoprogenitor cells from the BM microenvironment suppressed osteogenic differentiation and induced MDS and AML-like haematological findings. The present study evaluated the expression profiles of microRNAs (miRNAs) and DICER1 gene in BM-derived MSC of patients with AML (n=12), MDS (n=10) and healthy controls (HC) (n=8)...
December 2017: Leukemia Research
Kenko Azuma, Tomohiro Umezu, Satoshi Imanishi, Michiyo Asano, Seiichiro Yoshizawa, Seiichiro Katagiri, Kazuma Ohyashiki, Junko H Ohyashiki
Bone marrow mesenchymal stromal cells (MSCs), which support proliferation and differentiation of hematopoietic stem cells, may play a crucial role in the pathogenesis of myeloid neoplasms. To determine whether MSCs in myeloid neoplasms harbor distinct somatic mutations that may affect their function, we used a targeted gene sequencing panel containing 50 myeloid neoplasm-associated genes with coverage of ≥500. We compared the genetic alterations between MSCs and bone marrow hematopoietic (BM) cells from patients with acute leukemia (n=5) or myelodysplastic syndrome (MDS, n=5)...
November 2017: Leukemia Research
Atul Kumar, Trishna Anand, Jina Bhattacharyya, Amit Sharma, Bithiah Grace Jaganathan
Bone marrow (BM) microenvironment plays an important role in normal and malignant hematopoiesis. As a consequence of interaction with the leukemic cells, the stromal cells of the bone marrow become deregulated in their normal function and gene expression. In our study, we found that mesenchymal stem cells (MSC) from BM of chronic myeloid leukemia (CML) patients have defective osteogenic differentiation and on interaction with K562 CML cells, the normal MSC showed reduced osteogenic differentiation. On interaction with K562 cells or its secreted factors, MSC acquired phenotypic abnormalities and secreted high levels of IL6 through NFκB activation...
September 30, 2017: Journal of Cell Communication and Signaling
Kyu-Hyun Han, Ae-Kyeong Kim, Min-Hee Kim, Do-Hyung Kim, Ha-Nl Go, Donglim Kang, Jong Wook Chang, Soon Won Choi, Kyung-Sun Kang, Dong-Ik Kim
The aim of the present study was to investigate protein profiles of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) cultured in normoxic (21% O2 ) and hypoxic (1% O2 ) conditions, and evaluate oxygenation effects on angiogenesis in an ischemic hindlimb mouse model using a modified ischemic scoring system. Hypoxic conditions did not change the expression of phenotypic markers and increased adipogenesis and chondrogenesis. Epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), TGF-β RII, and vascular endothelial growth factor (VEGF) were upregulated in the conditioned medium of hypoxic hUCB-MSCs, which are commonly related to angiogenesis and proliferation of biological processes by Gene Ontology...
December 2017: Tissue & Cell
Juliana Barrera-Ramirez, Jessie R Lavoie, Harinad B Maganti, William L Stanford, Caryn Ito, Mitchell Sabloff, Marjorie Brand, Michael Rosu-Myles, Yevgeniya Le, David S Allan
Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified. Of the five candidate miRs identified by differential packaging in exosomes, only miR-26a-5p and miR-101-3p were significantly increased in AML-derived samples while miR-23b-5p, miR-339-3p and miR-425-5p were significantly decreased...
September 16, 2017: Stem Cell Reviews
Stella Genitsari, Eftichia Stiakaki, Chryssoula Perdikogianni, Georgia Martimianaki, Iordanis Pelagiadis, Margarita Pesmatzoglou, Maria Kalmanti, Helen Dimitriou
OBJECTIVE: Mesenchymal Stromal Cells (MSC) have a supportive role in hematopoiesis and as components of the bone marrow microenvironment may present alterations during ALL and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSC at ALL diagnosis and treatment and their effect on MSC qualitative properties. MATERIALS AND METHODS: Immunophenotypic characterization, evaluation of clonogenicity and proliferative capacity were performed...
September 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
Asima Tayyeb, Naveed Shahzad, Gibran Ali
INTRODUCTION: Mesenchymal stem cells (MSCs) have been publicized to ameliorate kidney injury both in vitro and in vivo. However, very less is known if MSCs can be differentiated towards renal lineages and their further application potential in kidney injuries. MATERIALS AND METHODS: The present study developed a conditioning system of growth factors fibroblast growth factor 2, transforming growth factor-β2, and leukemia inhibitory factor for in vitro differentiation of MSCs isolated from different sources towards nephrogenic lineage...
July 2017: Iranian Journal of Kidney Diseases
Djamel Aggoune, Nathalie Sorel, Marie-Laure Bonnet, Jean-Michel Goujon, Karin Tarte, Olivier Hérault, Jorge Domenech, Delphine Réa, Laurence Legros, Hyacinthe Johnson-Ansa, Philippe Rousselot, Emilie Cayssials, Agnès Guerci-Bresler, Annelise Bennaceur-Griscelli, Jean-Claude Chomel, Ali G Turhan
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG...
September 2017: Leukemia Research
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
July 6, 2017: Oncotarget
Yuan Ji, Yongbin Ma, Xiang Chen, Xianyan Ji, Jianyi Gao, Lei Zhang, Kai Ye, Fuhao Qiao, Yao Dai, Hui Wang, Xiangmei Wen, Jiang Lin, Jiabo Hu
Human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSCs) are able to inhibit proliferation of leukemia cells. Microvesicles released from human embryonic stem cell derived-mesenchymal stem cells (hESC‑MSC‑MVs) might play an important part in antitumor activity. Microvesicles were isolated by ultracentrifugation and identified under a scanning electron microscopy and transmission electron microscope separately. After 48-h cocultured with hESC‑MSCs and hESC‑MSC‑MVs, the number of K562 and HL60 was counted and tumor cell viability was measured by CCK8 assay...
August 2017: Oncology Reports
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
June 6, 2017: Stem Cell Reports
B de Rooij, R Polak, F Stalpers, R Pieters, M L den Boer
No abstract text is available yet for this article.
July 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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