scholarly journals Effect of Extracellular Vesicles Derived From Mesenchymal Stem Cells on K-562 Leukemia Cell Line

2018 ◽  
Vol 20 (5) ◽  
Author(s):  
Hajar Mardani Valandani ◽  
Naser Amirizadeh ◽  
Mahin Nikougoftar ◽  
Majid Safa ◽  
Roohollah Mirzaee Khalilabadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Line ◽  
Extracellular Vesicles ◽  
Leukemia Cell ◽  
Leukemia Cell Line

scholarly journals Acute Leukemia Induces Senescence and Impaired Osteogenic Differentiation in Mesenchymal Stem Cells Endowing Leukemic Cells with Functional Advantages

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Ximena Bonilla ◽  
Natalia-Del Pilar Vanegas ◽  
Jean Paul Vernot
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Line ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Hematopoietic Stem ◽  
Reh Cells

Mesenchymal stem cells (MSC) constitute an important cell population of the bone marrow hematopoietic niche that supports normally hematopoietic stem cells (HSC) but eventually also leukemic cells. The alterations that occur in the MSC under leukemic stress are not well known. To deepen on this topic, we have used an in vitro model of the leukemic niche (LN) by coculturing MSC with an acute lymphocytic leukemia cell line (REH) and proceeded to evaluate MSC characteristics and functions. We found that leukemic cells induced in MSC a significant increase both in senescence-associated β-galactosidase activity and in p53 gene expression. MSC in the LN also showed a persistent production of cytoplasmic reactive oxygen species (ROS) and a G2/M phase arrest of the cell cycle. Another acute leukemic cell line (SUP-B15) produced almost the same effects on MSC. REH cells adhere strongly to MSC possibly as a result of an increased expression of the adhesion molecules VCAM-1, ICAM-1, and CD49e in MSC and of CD49d in REH cells. Although mesensphere formation was normal or even increased, multipotent differentiation capacity was impaired in MSC from the LN. A REH-conditioned medium was only partially (about 50%) capable of inducing the same changes in MSC, suggesting that cell-to-cell contact is more efficient in inducing these changes. Despite these important effects on MSC in the LN, REH cells increased their cell adhesion, proliferation rate, and directed-migration capacity. In conclusion, in this in vitro LN model, leukemic cells affect importantly the MSC, inducing a senescence process that seems to favour leukemic cell growth.

Identification and Purification of Leukemic Stem-Like Cells in Acute Myeloid Leukemia Cell Line

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4734-4734
Author(s):  
Miaorong She ◽  
Xingqing Niu ◽  
Xilin Chen ◽  
Guo Kunyuan ◽  
Maohua Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Cell Line ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Leukemic Stem Cells ◽  
Self Renewal ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) is initiated and maintained by a rare population of (leukemic stem cells) LSCs. LSCs play the central role in the relapse and refractory of AML and highlight the critical need for the new therapeutic strategies to directly target the LSC population for ultimately curing leukemia which is it is important to identify and study LSCs. However, relatively little is known about the unique molecular mechanisms of survival and self-renewal of LSCs because of very small number of LSCs in bone marrow. In this study, we investigated whether established leukemia cell lines contain LSCs. We showed that leukemia cell line contain leukemic stem-like cells which have been phenotypically restricted within the CD34+CD38− fraction. We demonstrated that CD34+CD38− cells could generate CD34+CD38+ cells in culture medium and had proliferation function. Moreover, CD34+CD38− cells had self-renewal potential both in vitro soft agar colonies formation assay and in vivo NOD/SCID mouse xenotransplant model serial transplantation. Furthermore, CD34+CD38− cells isolated from leukemia cell line were found resistant to conventional chemotherapy and NK cells-mediated cytotoxicity and these were related to up-regulation of ABCG2 and MRP-1 and antiapoptotic proteins of Bcl2. Down-regulation of NKG2D ligand also played a critical role in NK cytotoxicity resistance. Taken together, our studies provide a novel cell model for leukemic stem cells research. Our data also shed light on mechanism of double resistant to resistant to chemotherapy and NK cell immunotherapy, which was helpful for developing novel effective strategies for LSCs.

scholarly journals NK Cells from Human Pluripotent Stem Cells for Immunotherapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4955-4955
Author(s):  
Hiroyuki Maysubara ◽  
Akira Niwa ◽  
Tatsutoshi Nakahata ◽  
Megumu K Saito
Keyword(s):  
Stem Cells ◽  
Nk Cells ◽  
Cell Line ◽  
Pluripotent Stem Cells ◽  
Nk Cell ◽  
Leukemia Cell ◽  
Defined Medium ◽  
Leukemia Cell Line ◽  
Chemically Defined Medium ◽  
Free Condition

Abstract Natural Killer (NK) cells are a one of innate lymphocytes and show cytotoxicity against tumour cells without prior antigen specific stimulation. . NK cells can demonstrate stronger cytotoxicity than T cells in the absence of MHC Class I, and survive short lifespan from several weeks to one month. It suggested that NK cells show low risk of cytokine long-term secretion inside patient's body. Previous studies have developed peripheral blood mononuclear cells (PBMC) derived NK cells expansions or NK cells differentiation from cord blood (CB) cells for immunotherapy. Expansion trial using K562 tumor cell line, or with IL-15, or an anti-tumor antibody dasatinib is not sufficient to obtain NK cells with high cytotoxicity.More recently, NK cells induction from human pluripotent stem cells (hPSCs), taking the advantage of their unlimited growth potential, has been reported. Although previous studies regarding hPSC-derived NK cells seems impressive and successful, most systems used a bovine and human serum, which might result in the unstable yield and efficiency in the production of Hematopoietic progenitor cells (HPCs) and NK cells for immunotherapy. To resolve those problems, we tried to induce functional NK cells from hPSCs in xeno and serum free condition. This study used three hPSC cell lines; human ES cell (cell line: KhES1) and iPS cells (cell line: 409B2 and CB-A11) to check reproducibility. To differentiate hPSCs into hematopoietic cells, changed cytokine combinations and chemically defined medium in step-wise manner. We first induced HPC from hPSCs over 90% purity by 12 days culture. At this point, we selected two media to induce NK cells. We compared serum-containing medium that previous report used (Medium A) and chemically-defined medium (Medium B) by evaluating the differentiation efficiency and function of NK cells. NK cell marker CD56 (NCAM) was gradually expressed after additional 16 days culture (28 days of differentiation). Until hPSC-derived NK cells were maturated, we traced the expression of NK specific markers and transcriptional factors. On day48, the frequency of CD56 positive cells showed no significant differences between medium A (79.15 ± 5.30%) and medium B (80.90 ± 1.27%). In both conditions, NK cells expressed specific receptors such as CD161, NKG2D, killer immunoglobulin-like receptors (KIRs), NKG2a (CD94/CD159a heterodimeric inhibitory receptor), NKp44 and NKp46. hPSC-derived NK cells showed the compatible size and morphology to NK cells isolated from peripheral blood NK (PB-NK) cells: their nucleus was kidney-like shape and cytoplasm contained azurophilic granules. For functional assay, leukemia cell line K562 was incubated with 51 chromium (51Cr) for 1 hour at 37 degrees. After that, K562 was co-cultured with purified CD56 positive hPSC-derived NK cells for 4 hours at 37 degrees. The cytotoxic activity of NK cells was confirmed by 51Cr release from K562. PBMC-NK cells showed 49.65 ± 3.46% of killing activity against K562 target cells, while the killing potential of PSC-derived NK cell showed killing potential against K562 cells (Medium A: 25.4 ± 5.52%, Medium B: 23.25 ± 9.26%) which was slightly lower than that of PB-NK cells. Next trial, we are going to transplant hPSC-derived NK cells into immune deficiency mice. In detail, this mice was infected luciferase expressed K562. Using IVIS imaging system to detect intensity of luciferase, we characterized hPSC-derived NK cells potential in vivo. Here we have developed a novel and robust method to facilitate efficient NK cells differentiation in serum and xeno-free condition in all clones. They showed similar phenotypes compare to PBMC derived NK cells in terms of morphology, surface markers, translational factors and cytotoxicity against leukemia cell line K562 in vitro. This technology expected to be applicable not only to immunotherapy but also to model studies of the NK cells associating diseases. Disclosures No relevant conflicts of interest to declare.

Characteristics of insulin receptors and insulin action in human myelogenous leukemia cell line K-562

Diabetes ◽  
1985 ◽  
Vol 34 (4) ◽  
pp. 347-352 ◽  
Author(s):  
T. Yamanouchi ◽  
T. Tsushima ◽  
Y. Akanuma ◽  
M. Kasuga ◽  
H. Mizoguchi ◽  
...  
Keyword(s):  
Cell Line ◽  
Insulin Action ◽  
Leukemia Cell ◽  
Insulin Receptors ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line

Antioxidant effects and in vitro cytotoxicity on human cancer cell lines of flavonoid-rich Flamboyant (Delonix regia (Bojer) Raf.) flower extract

2020 ◽  
Vol 21 ◽  
Author(s):  
Putthiporn Khongkaew ◽  
Phanphen Wattanaarsakit ◽  
Konstantinos I. Papadopoulos ◽  
Watcharaphong Chaemsawang
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Flower Extract ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Murine Leukemia Cell ◽  
Dose Dependent

Background: Cancer is a noncommunicable disease with increasing incidence and mortality rates both worldwide and in Thailand. Its apparent lack of effective treatments is posing challenging public health issues. Introduction: Encouraging research results indicating probable anti-cancer properties of the Delonix regia flower extract (DRE) have prompted us to evaluate the feasibility of developing a type of product for future cancer prevention or treatment. Methods and Results: In the present report, using High Performance Liquid Chromatography (HPLC), we demonstrate in the DRE, the presence of high concentrations of three identifiable flavonoids, namely rutin 4.15±0.30 % w/w, isoquercitrin 3.04±0.02 %w/w, and myricetin 2.61±0.01 % w/w respectively while the IC50 of DPPH and ABTS assay antioxidation activity was 66.88±6.30 µg/ml and 53.65±7.24 µg/ml respectively. Discussion: Our cancer cell line studies using the MTT assay demonstrated DREs potent and dose dependent inhibition of murine leukemia cell line (P-388: 35.28±4.07% of cell viability remaining), as well as of human breast adenocarcinoma (MCF-7), human cervical carcinoma (HeLa), human oral cavity carcinoma (KB), and human colon carcinoma (HT-29) cell lines in that order of magnitude. Conclusion: Three identifiable flavonoids (rutin, isoquercitrin and myricetin) with high antioxidation activity and potent and dose dependent inhibition of murine leukemia cell line and five other cancer cell lines were documented in the DRE. The extract’s lack of cytotoxicity in 3 normal cell lines is a rare advantage not usually seen in current antineoplastic agents. Yet another challenge of the DRE was its low dissolution rate and long-term storage stability, issues to be resolved before a future product can be formulated.

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