Mesenchymal stem cells promote leukaemic cells aberrant phenotype from B-cell acute lymphoblastic leukaemia

Rodríguez-Pardo, Viviana Marcela; Aristizabal, José A.; Jaimes, Diana; Quijano, Sandra; Reyes, Iliana De los; Herrera, María Victoria; Solano, Julio; Vernot, Jean-Paul

doi:10.1016/j.hemonc.2013.09.002

Cited by 7 publications

(7 citation statements)

References 51 publications

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“…To obtain MSC, bone marrow (BM) samples were obtained with the support of the Department of Orthopedics and Traumatology of Hospital Universitario San Ignacio (Bogota, Colombia) from volunteer donors (undergoing hip replacement surgery) after signing the informed consent form approved by the Hospital Ethics Committee. BM-MSC were isolated and cultured as previously published (14, 15), and they were used in passages 3–5 for a 3D culture system. The BM-MSC phenotype was assessed by flow cytometry with a FACS Aria-II cytometer (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

“…These cells, which express common mesenchymal antigens such as CD73 and CD105 or particular antigens (according to the subtype) such as CD146, CXCL-12 (CAR cells), nestin and leptin receptor (LepR), have in common the secretion of two determining soluble factors for HSC: CXCL-12 (SDF-1) and SCF (11, 12), which participate in maintaining the viability, self-renewal and mobilization of hematopoietic cells. Some MSC populations of the vascular niche are more resistant to chemotherapy and induce the regeneration of HSC after exposure to cytotoxic agents (13), and in vitro, they can maintain the phenotypic and functional characteristics of HSC of umbilical cord blood and leukemic cells (14, 15).…”

Section: Introductionmentioning

confidence: 99%

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Generation of Organotypic Multicellular Spheres by Magnetic Levitation: Model for the Study of Human Hematopoietic Stem Cells Microenvironment

Mejía-Cruz

Barreto-Durán

Pardo-Pérez

et al. 2019

IJSC

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Background and Objective The characteristics of human hematopoietic stem cells are conditioned by the microenvironment of the bone marrow, where they interact with other cell populations, such as mesenchymal stem cells and endothelial cells; however, the study of this microenvironment is complex. The objective of this work was to develop a 3D culture system by magnetic levitation that imitates the microenvironment of human HSC. Methods and Results Human bone marrow-mesenchymal stem cells, umbilical cord blood-hematopoietic stem cells and a non-tumoral endothelial cell line (CC2811, Lonza ® ) were used to develop organotypic multicellular spheres by the magnetic levitation method. We obtained viable structures with an average sphericity index greater than 0.6, an average volume of 0.5 mm 3 and a percentage of aggregation greater than 70%. Histological studies of the organotypic multicellular spheres used hematoxylin and eosin stains, and an evaluation of vimentin expression by means of immunohistochemistry demonstrated an organized internal structure without picnotic cells and a high expression of vimentin. The functional capacity of human hematopoietic stem cells after organotypic multicellular spheres culture was evaluated by multipotency tests, and it was demonstrated that 3D structures without exogenous Flt3L are autonomous in the maintenance of multipotency of human hematopoietic stem cells. Conclusions We developed organotypic multicellular spheres from normal human cells that mimic the microenvironment of the human hematopoietic stem cells. These structures are the prototype for the development of complex organoids that allow the further study of the biology of normal human stem cells and their potential in regenerative medicine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Generation of Organotypic Multicellular Spheres by Magnetic Levitation: Model for the Study of Human Hematopoietic Stem Cells Microenvironment

Mejía-Cruz

Barreto-Durán

Pardo-Pérez

et al. 2019

IJSC

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“…MSCs are known for its ability as immune modulator capable of regulating proliferation and differentiation of immune cells such as macrophages, B and T cells, NK cells, and even mast cells [ 30 ]. Studies suggested that MSCs promote cellular proliferation and maintenance of either normal or malignant hematopoietic cells in direct co-culture [ 31 , 32 ]. Our results indicated TRAIL secretion by ADMSCs induced cellular inhibition of hematopoietic malignant cell noticed in REH line shown by Figure 4 B.…”

Section: Discussionmentioning

confidence: 99%

Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells

et al. 2014

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BackgroundTumour homing capacity of engineered human adipose-derived mesenchymal stromal cells (ADMSCs) expressing anti-tumour agents might be the key for a much safer and yet efficient targeted tumour therapy. However, ADMSCs exhibit resistant to most gene transfection techniques and the use of highly efficient viral vectors has several disadvantages primarily concerning safety risk. Here, we optimized the use of highly efficient and safe nucleofection-based transfection using plasmid encoded for TNF-Related Apoptosis Inducing Ligand (TRAIL) into ADMSCs and investigated the potential anti-tumourigenic of TRAIL-expressing ADMSCs (ADMSCs-TRAIL) on selected cancer models in vitro.MethodsDifferent concentration of TRAIL-encoded plasmid and ADMSCs were nucleofected and the percentage of fluorescence cells were analyzed to determine the optimal condition. TRAIL protein and mRNA were validated in nucloeofected ADMSCs using ELISA and RT-PCR respectively. Evaluation of TRAIL specific death receptors were performed on both tumours (A549/lung tumour, LN18/glioblastoma and HepG2/hepatocellular carcinoma) and haematological malignant lines (REH/acute lymphocytic leukaemia, K562/chronic myelogenous leukaemia and KMS-28BM/multiple myeloma) using flow cytometry. ADMSCs-TRAIL was subsequently assessed for anti-tumourigenic properties using both proliferation assay (MTS assay) and apoptosis assay (Annexin-V / Propidium Iodide staining).ResultsNucleofection showed increased total plasmid concentration (2 μg to 8 μg) resulted in significantly higher reporter expression (11.33% to 39.7%) with slight reduction on cells viability (~10%). ADMSCs-TRAIL significantly inhibited ~50% of cell proliferation in LN18, signifying sensitivity of the cell to ADMSCs-TRAIL mediated inhibition. Inhibition of both tumour and malignant lines proliferation by ADMSCs-TRAIL conditioned medium noticed in HepG2, A549 and REH respectively, whereas K562 and KMS-28BM malignant lines exhibit resistant to ADMSCs-TRAIL mediated inhibition. Moreover, we found that native ADMSCs alone were capable of inducing apoptosis in both LN18 and HepG2 tumour lines, despite substantial increased on the percentage of apoptosis by ADMSCs-TRAIL.ConclusionADMSCs-TRAIL selectively inhibit cancer model and markedly induces apoptosis. Through investigation of the specific TRAIL death receptors expression, we saw that the receptors expression did influence the sensitivity of some but not all cancer lines to TRAIL-mediated inhibition. This study provides further insight into the anti-tumourigenic potential of ADMSCs-TRAIL on different cancer models.

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“…Hierarchical cluster analysis of these surface markers shows that, after co-culture with MSCs, an association between pre-pre-B-cells from control patients (Ct) and B-ALLBMMNCs gradually forms. However, no association between these cell groups has been observed after their co-culture in the absence of BMMSCs [ 51 ].…”

Section: Characterization Of Msc-b Cells Interactionsmentioning

confidence: 99%

Interaction between Mesenchymal Stem Cells and B-Cells

Fan

Chen

et al. 2016

IJMS

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Mesenchymal stem cells (MSCs) are multipotent; non-hematopoietic stem cells. Because of their immunoregulatory abilities; MSCs are widely used for different clinical applications. Compared with that of other immune cells; the investigation of how MSCs specifically regulate B-cells has been superficial and insufficient. In addition; the few experimental studies on this regulation are often contradictory. In this review; we summarize the various interactions between different types or states of MSCs and B-cells; address how different types of MSCs and B-cells affect this interaction and examine how other immune cells influence the regulation of B-cells by MSCs. Finally; we hypothesize why there are conflicting results on the interaction between MSCs and B-cells in the literature.

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Mesenchymal stem cells promote leukaemic cells aberrant phenotype from B-cell acute lymphoblastic leukaemia

Cited by 7 publications

References 51 publications

Generation of Organotypic Multicellular Spheres by Magnetic Levitation: Model for the Study of Human Hematopoietic Stem Cells Microenvironment

Generation of Organotypic Multicellular Spheres by Magnetic Levitation: Model for the Study of Human Hematopoietic Stem Cells Microenvironment

Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells

Interaction between Mesenchymal Stem Cells and B-Cells

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