Research Article

Effect of Rat Bone Marrow Derived-Mesenchymal Stem Cells on Granulocyte Differentiation of Mononuclear Cells as Preclinical Agent in Cellbased Therapy

Author(s): Ezzatollah Fathi, Sheyda Azarbad, Raheleh Farahzadi*, Sara Javanmardi and Ilja Vietor*

Volume 22, Issue 2, 2022

Published on: 20 July, 2021

Page: [152 - 161] Pages: 10

DOI: 10.2174/1566523221666210519111933

Price: $65


Background: Bone marrow mononuclear cells (BM-MNCs), as a collection of hematopoietic and mesenchymal stem cells (MSCs), are capable of producing all blood cell lineages. The use of cytokines, growth factors or cells capable of secreting these factors will help in stimulating the proliferation and differentiation of these cells into mature cell lines. On the other hand, MSCs are multipotent stromal cells that can be differentiated into various cell lineages. Moreover, these cells can control the process of hematopoiesis by secreting cytokines and growth factors. The present study aimed to investigate the effect of BM-derived MSCs on the differentiation of MNCs based on the assessment of cell surface markers by flow cytometry analysis.

Methods: For this purpose, the MNCs were purified from rat BM using density gradient centrifugation. Thereafter, they were cultured, expanded, and characterized. Next, BM-derived-MSCs were cocultured with MNCs, and then were either cultured MNCs alone (control group) or co-cultured MNCs with BM-derived-MSCs (experimental group). Finally, they were collected on day 7 and subjected to flow cytometry analysis for granulocyte markers and ERK protein investigation.

Results: It was found that the expression levels of CD34, CD16, CD11b, and CD18 granulocyte markers as well as protein expression of ERK have significantly increased in the experimental group compared to the control group.

Conclusion: Therefore, it can be concluded that MSCs could affect the granulocyte differentiation of MNCs via ERK protein expression, which is a key component of the ERK signaling pathway.

Keywords: Mesenchymal stem cells, granulocyte differentiation, mononuclear cells, cell based-therapy, clinical agent, bonemarrow mononuclear cells.

Graphical Abstract
Saleh M, Shamsasanjan K, Movassaghpourakbari A, Akbarzadehlaleh P, Molaeipour Z. The impact of mesenchymal stem cells on differentiation of hematopoietic stem cells. Adv Pharm Bull 2015; 5(3): 299-304.
[] [PMID: 26504750]
Mobarak H, Fathi E, Farahzadi R, Zarghami N, Javanmardi S. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells. Vet Res Commun 2017; 41(1): 41-7.
[] [PMID: 27943151]
Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal 2011; 9(1): 12-26.
[] [PMID: 21569606]
Wu K-H, Wu H-P, Chan C-K, Hwang SM, Peng CT, Chao YH. The role of mesenchymal stem cells in hematopoietic stem cell transplantation: from bench to bedsides. Cell Transplant 2013; 22(4): 723-9.
[] [PMID: 23068433]
Weiskopf K, Schnorr PJ, Pang WW, et al. Myeloid cell origins, differentiation, and clinical implications. Microbiol Spectr 2016; 4(5): 857-75.
[PMID: 27763252]
Gholizadeh-Ghaleh Aziz S, Fathi E, Rahmati-Yamchi M, Akbarzadeh A, Fardyazar Z, Pashaiasl M. An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering. Artif Cells Nanomed Biotechnol 2017; 45(4): 765-74.
[] [PMID: 27684534]
Ebrahimi T, Abasi M, Seifar F, et al. Transplantation of stem cells as a potential therapeutic strategy in neurodegenerative disorders. Curr Stem Cell Res Ther 2021; 16(2): 133-44.
[] [PMID: 32598273]
Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8(9): 726-36.
[] [PMID: 19172693]
Fathi E, Sanaat Z, Farahzadi R. Mesenchymal stem cells in acute myeloid leukemia: a focus on mechanisms involved and therapeutic concepts. Blood Res 2019; 54(3): 165-74.
[] [PMID: 31730689]
Minguell JJ, Conget P, Erices A. Biology and clinical utilization of mesenchymal progenitor cells. Braz J Med Biol Res 2000; 33(8): 881-7.
[] [PMID: 10920429]
Fathi E, Farahzadi R, Javanmardi S, Vietor I. L-carnitine extends the telomere length of the cardiac differentiated CD117+- expressing stem cells. Tissue Cell 2020; 67: 101429.
[] [PMID: 32861877]
Briquet A, Dubois S, Bekaert S, Dolhet M, Beguin Y, Gothot A. Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages. Haematologica 2010; 95(1): 47-56.
[] [PMID: 19713224]
Nikkhah H, Safarzadeh E, Shamsasenjan K, et al. The effect of bone marrow mesenchymal stem cells on the granulocytic differentiation of HL-60 cells. Turk J Haematol 2018; 35(1): 42-8.
[] [PMID: 28611013]
Chen F, Zhou K, Zhang L, et al. Mesenchymal stem cells induce granulocytic differentiation of acute promyelocytic leukemic cells via IL-6 and MEK/ERK pathways. Stem Cells Dev 2013; 22(13): 1955-67.
[] [PMID: 23391335]
Robinson SN, Ng J, Niu T, et al. Superior ex vivo cord blood expansion following co-culture with bone marrow-derived mesenchymal stem cells. Bone Marrow Transplant 2006; 37(4): 359-66.
[] [PMID: 16400333]
Montazersaheb S, Fathi E, Farahzadi R. Cytokines and signaling pathways involved in differentiation potential of hematopoietic stem cells towards natural killer cells. Tissue Cell 2021; 70: 101501.
[] [PMID: 33578272]
Aqmasheh S, Shamsasanjan K, Akbarzadehlaleh P, Pashoutan Sarvar D, Timari H. Effects of mesenchymal stem cell derivatives on hematopoiesis and hematopoietic stem cells. Adv Pharm Bull 2017; 7(2): 165-77.
[] [PMID: 28761818]
Fathi E, Farahzadi R, Valipour B, 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.
[] [PMID: 31009502]
Fathi E, Vietor I. Mesenchymal stem cells promote caspase expression in Molt-4 leukemia cells via GSK-3α/β and ERK1/2 signaling pathways as a therapeutic strategy. Curr Gene Ther 2021; 21(1): 81-8.
[] [PMID: 33019931]
Farahzadi R, Mesbah-Namin SA, Zarghami N, Fathi E. L-carnitine effectively induces hTERT gene expression of human adipose tissue-derived mesenchymal stem cells obtained from the aged subjects. Int J Stem Cells 2016; 9(1): 107-14.
[] [PMID: 27426092]
Farahzadi R, Fathi E, Vietor I. Mesenchymal stem cells could be considered as a candidate for further studies in cell-based therapy of Alzheimer’s disease via targeting the signaling pathways. ACS Chem Neurosci 2020; 11(10): 1424-35.
[] [PMID: 32310632]
Fathi E, Valipour B, Sanaat Z, Nozad Charoudeh H, Farahzadi R. Interleukin-6, -8, and TGF-β secreted from mesenchymal stem cells show functional role in reduction of telomerase activity of Leukemia cell via Wnt5a/β-catenin and P53 pathways. Adv Pharm Bull 2020; 10(2): 307-14.
[] [PMID: 32373501]
Fathi E, Farahzadi R, Vietor I, Javanmardi S. Cardiac differentiation of bone-marrow-resident c-kit+ stem cells by L-carnitine increases through secretion of VEGF, IL6, IGF-1, and TGF- β as clinical agents in cardiac regeneration. J Biosci 2020; 45(1): 1-11.
[] [PMID: 32713855]
Fathi E, Farahzadi R, Valipour B. Alginate/gelatin encapsulation promotes NK cells differentiation potential of bone marrow resident C-kit+ hematopoietic stem cells. Int J Biol Macromol 2021; 177: 317-27.
[] [PMID: 33621568]
Montazersaheb S, Kazemi M, Nabat E, Nielsen PE, Hejazi MS. Downregulation of TdT expression through splicing modulation by antisense peptide nucleic acid (PNA). Curr Pharm Biotechnol 2019; 20(2): 168-78.
[] [PMID: 30727883]
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): 1612-9.
[] [PMID: 28058860]
Fathi E, Valipour B, Farahzadi R. Targeting the proliferation inhibition of chronic myeloid Leukemia cells by bone marrow derived-mesenchymal stem cells via ERK pathway as a therapeutic strategy. Acta Med Iran 2020; 58(5): 199-206.
Uccelli A, Pistoia V, Moretta L. Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol 2007; 28(5): 219-26.
[] [PMID: 17400510]
Walenda T, Bork S, Horn P, et al. Co-culture with mesenchymal stromal cells increases proliferation and maintenance of haematopoietic progenitor cells. J Cell Mol Med 2010; 14(1-2): 337-50.
[] [PMID: 19432817]
Park CW, Kim KS, Bae S, et al. Cytokine secretion profiling of human mesenchymal stem cells by antibody array. Int J Stem Cells 2009; 2(1): 59-68.
[] [PMID: 24855521]
Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998; 176(1): 57-66.
[<57:AID-JCP7>3.0.CO;2-7] [PMID: 9618145]
Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res 2000; 9(6): 841-8.
[] [PMID: 11177595]
Luo H, Li Q, O’Neal J, Kreisel F, Le Beau MM, Tomasson MH. c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Blood 2005; 106(7): 2452-61.
[] [PMID: 15972450]
Huang M-J, Cheng YC, Liu C-R, Lin S, Liu HE. A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemia. Exp Hematol 2006; 34(11): 1480-9.
[] [PMID: 17046567]
Ganta C, Chiyo D, Ayuzawa R, et al. Rat umbilical cord stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation. Cancer Res 2009; 69(5): 1815-20.
[] [PMID: 19244122]
Secchiero P, Zorzet S, Tripodo C, et al. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin’s lymphoma xenografts. PLoS One 2010; 5(6): e11140.
[] [PMID: 20585401]
Eggenhofer E, Luk F, Dahlke MH, Hoogduijn MJ. The life and fate of mesenchymal stem cells. Front Immunol 2014; 5: 148-52.
[] [PMID: 24904568]
Christensen JE, Andreasen SØ, Christensen JP, Thomsen AR. CD11b expression as a marker to distinguish between recently activated effector CD8(+) T cells and memory cells. Int Immunol 2001; 13(4): 593-600.
[] [PMID: 11282998]
Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 1990; 75(5): 1037-50.
[] [PMID: 1968349]
Leong JW, Chase JM, Romee R, et al. Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells. Biol Blood Marrow Transplant 2014; 20(4): 463-73.
[] [PMID: 24434782]
Tirelli V, Ghinassi B, Migliaccio AR, et al. Phenotypic definition of the progenitor cells with erythroid differentiation potential present in human adult blood. Stem Cells Int 2011; 2011: 602483.
[] [PMID: 21961017]
Rasmusson I, Ringdén O, Sundberg B, Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76(8): 1208-13.
[] [PMID: 14578755]
Blalock W, Pearce M, Steelman L, et al. A conditionally-active form of MEK1 abrogates cytokine-dependency in human and mouse hematopoietic cells. Oncogene 2000; 19: 526-36.
[] [PMID: 10698522]
Herrera R, Hubbell S, Decker S, Petruzzelli L. A role for the MEK/MAPK pathway in PMA-induced cell cycle arrest: modulation of megakaryocytic differentiation of K562 cells. Exp Cell Res 1998; 238(2): 407-14.
[] [PMID: 9473349]
Miranda MB, McGuire TF, Johnson DE. Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines. Leukemia 2002; 16(4): 683-92.
[] [PMID: 11960350]
Miranda MB, Xu H, Torchia JA, Johnson DE. Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway. Leuk Res 2005; 29(11): 1293-306.
[] [PMID: 16164983]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy