Targeting the Proliferation Inhibition of Chronic Myeloid Leukemia Cells by Bone Marrow Derived-Mesenchymal Stem Cells via ERK Pathway as a Therapeutic Strategy
Bone marrow-derived mesenchymal stem cells (BMSCs) are of specific attention due to their potential clinical use in cell transplantation. These cells could secrete cytokines and growth factors upon stimulation or suppression in regenerative medicine. This study was to evaluate the influence of BMSCs on the proliferation of K562 cells as chronic myeloid leukemia (CML) cell lines through the ERK pathway. For this purpose, BMSCs were extracted from Rattus Norvegicus and were co-cultured with K562 cells. In the following, at the end of the 7th day, the K562 cell was collected and subjected to ERK protein expression measurement as well as ERK gene expression by flow-cytometry and real time-PCR, respectively. Also, the cell proliferation and PDT of K562 cells were measured in the control and experimental groups. The results were shown that BMSCs were positive for mesenchymal (CD44 and CD90) and negative for hematopoietic (CD34 and CD56) markers. In addition, it was shown that BMSCs mediated CML cell line proliferation arrest via a significant reduction of the ERK protein expression in the co-culture groups versus in the K562 cell line control group. Taken together, the data concluded that the co-culture of BMSCs with CML cell lines could secrete a substantial amount of cytokines and growth factors, thus inhibiting the proliferation of CML cell lines via the ERK signaling pathway. The identity of molecules, cytokines, and growth factors involved in the anti-proliferative effect of bone marrow-derived MSCs require further investigation, and this effect could important in the basic experimental study as a therapeutic strategy.
2. Amirkhani MA, Shoae-Hassani A, Soleimani M, Hejazi S, Ghalichi L, and Nilforoushzadeh MA. Rejuvenation of facial skin and improvement in the dermal architecture by transplantation of autologous stromal vascular fraction: a clinical study. Bioimpacts 2016;6(3):149-154.
3. Zhang HM and Zhang LS. Influence of human bone marrow mesenchymal stem cells on proliferation of chronic myeloid leukemia cells. Ai Zheng 2009;28(1):29-32.
4. Tong CK, Vellasamy S, Tan BC, et al. Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method. Cell Biol Int 2011;35(3):221-6.
5. Lotfinegad P, Shamsasenjan K, Movassaghpour A, Majidi J, and Baradaran B. Immunomodulatory nature and site specific affinity of mesenchymal stem cells: a hope in cell therapy. Adv Pharm Bull 2014;4(1):5-13.
6. Fathi E, Farahzadi R, Valipour B, and Sanaat Z. Cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis and change cell cycle distribution of K562 cell line as clinical agent in cell transplantation. PloS one 2019;14(4):e0215678.
7. Fathi E, Farahzadi R, and Sheikhzadeh N. Immunophenotypic characterization, multi-lineage differentiation and aging of zebrafish heart and liver tissue-derived mesenchymal stem cells as a novel approach in stem cell-based therapy. Tissue and Cell 2019.
8. Fathi E and Farahzadi R. Enhancement of osteogenic differentiation of rat adipose tissue-derived mesenchymal stem cells by zinc sulphate under electromagnetic field via the PKA, ERK1/2 and Wnt/beta-catenin signaling pathways. PLoS One 2017;12(3):e0173877.
9. Fathi E and Farahzadi R. Zinc Sulphate Mediates the Stimulation of Cell Proliferation of Rat Adipose Tissue-Derived Mesenchymal Stem Cells Under High Intensity of EMF Exposure. Biol Trace Elem Res 2017.
10. Mehdizadeh A, Somi MH, Darabi M, et al. Liposome-mediated RNA interference delivery against Erk1 and Erk2 does not equally promote chemosensitivity in human hepatocellular carcinoma cell line HepG2. Artif Cells Nanomed Biotechnol 2017;45(8):1612-1619.
11. le Coutre P, Reinke P, Neuhaus R, et al. BCR-ABL positive cells and chronic myeloid leukemia in immune suppressed organ transplant recipients. Eur J Haematol 2010;84(1):26-33.
12. Crawford L, Chan E, Aujay M, et al. Synergistic effects of proteasome inhibitor carfilzomib in combination with tyrosine kinase inhibitors in imatinib-sensitive and-resistant chronic myeloid leukemia models. Oncogenesis 2014;3(3):e90.
13. Foley SB, Hildenbrand ZL, Soyombo AA, et al. Expression of BCR/ABL p210 from a knockin allele enhances bone marrow engraftment without inducing neoplasia. Cell reports 2013;5(1):51-60.
14. Masamoto Y and Kurokawa M. Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers? Stem cell investigation 2018;5.
15. Azizidoost S, Babashah S, Rahim F, Shahjahani M, and Saki N. Bone marrow neoplastic niche in leukemia. Hematology 2014;19(4):232-8.
16. Saki N, Abroun S, Farshdousti Hagh M, and Asgharei F. Neoplastic bone marrow niche: hematopoietic and mesenchymal stem cells. Cell J 2011;13(3):131-6.
17. Tyndall A, Walker UA, Cope A, et al. Immunomodulatory properties of mesenchymal stem cells: a review based on an interdisciplinary meeting held at the Kennedy Institute of Rheumatology Division, London, UK, 31 October 2005. Arthritis Res Ther 2007;9(1):301.
18. Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, and Papamichail M. Interactions between human mesenchymal stem cells and natural killer cells. Stem Cells 2006;24(1):74-85.
19. Aggarwal S and Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005;105(4):1815-22.
20. Fonseka M, Ramasamy R, Tan BC, and Seow HF. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line). Cell Biol Int 2012;36(9):793-801.
21. Lewis TS, Shapiro PS, and Ahn NG. Signal transduction through MAP kinase cascades. Adv Cancer Res 1998;74:49-139.
22. Sebolt-Leopold JS and Herrera R. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 2004;4(12):937-47.
23. Ma L, Xu Z, Wang J, et al. Matrine inhibits BCR/ABL mediated ERK/MAPK pathway in human leukemia cells. Oncotarget 2017;8(65):108880.
24. Kogler G, Radke TF, Lefort A, et al. Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 2005;33(5):573-83.
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