Mesenchymal Stem Cells, Immune Cells and Tumor Cells Crosstalk: A Sinister Triangle in the Tumor Microenvironment

Author(s): Mahboobeh Razmkhah, Shabnam Abtahi, Abbas Ghaderi*.

Journal Name: Current Stem Cell Research & Therapy

Volume 14 , Issue 1 , 2019

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Abstract:

Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like cells which maintain self-renewability and pluripotency. Many studies have demonstrated the immunomodulatory effects of MSCs on the innate and adaptive immune cells. As a result of interactions with tumor cells, microenvironment and immune-stimulating milieu, MSCs contribute to tumor progression by several mechanisms, including sustained proliferative signal in cancer stem cells [CSCs], inhibition of tumor cell apoptosis, transition to tumor-associated fibroblasts [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal transition [EMT], suppression of immune responses, and consequential promotion of tumor metastasis. Here, we present an overview of the latest findings on Janusfaced roles that MSCs play in the tumor microenvironment [TME], with a concise focus on innate and adaptive immune responses.

Keywords: Mesenchymal stem cells, tumor microenvironment, immunomodulation, innate immune response, adaptive immune response, metastasis.

[1]
Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Bioscience reports 2015; 35(2): e00191.
[2]
Leach JK, Whitehead J. Materials-directed differentiation of mesenchymal stem cells for tissue engineering and regeneration. ACS Biomater Sci Eng 2018; 4(4): 1115-27.
[3]
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7.
[4]
Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018; 93(1): 19-31.
[5]
Hass R, Kasper C, Bohm 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: 12.
[6]
Gao F, Chiu SM, Motan DA, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis 2016; 7: e2062.
[7]
Burrello J, Monticone S, Gai C, Gomez Y, Kholia S, Camussi G. Stem cell-derived extracellular vesicles and immune-modulation. Front Cell Dev Biol 2016; 4: 83.
[8]
Wang M, Yuan Q, Xie L. Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application. Stem Cells Int 2018; 2018: 3057624.
[9]
Burr SP, Dazzi F, Garden OA. Mesenchymal stromal cells and regulatory T cells: The Yin and Yang of peripheral tolerance? Immunol Cell Biol 2013; 91(1): 12-8.
[10]
Schepers K, Fibbe WE. Unraveling mechanisms of mesenchymal stromal cell-mediated immunomodulation through patient monitoring and product characterization. Ann N Y Acad Sci 2016; 1370(1): 15-23.
[11]
English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 2013; 91(1): 19-26.
[12]
Dostert G, Mesure B, Menu P, Velot E. How Do Mesenchymal Stem Cells Influence or Are Influenced by Microenvironment through Extracellular Vesicles Communication? Front Cell Dev Biol 2017; 5: 6.
[13]
Whiteside TL. Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment. Semin Immunol 2018; 35: 69-79.
[14]
Pietras K, Ostman A. Hallmarks of cancer: Interactions with the tumor stroma. Exp Cell Res 2010; 316(8): 1324-31.
[15]
Sohni A, Verfaillie CM. Mesenchymal stem cells migration homing and tracking. Stem Cells Int 2013; 2013: 130763.
[16]
Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19(11): 1423-37.
[17]
Prantl L, Muehlberg F, Navone NM, et al. Adipose tissue-derived stem cells promote prostate tumor growth. Prostate 2010; 70(15): 1709-15.
[18]
Kucerova L, Matuskova M, Hlubinova K, Altanerova V, Altaner C. Tumor cell behaviour modulation by mesenchymal stromal cells. Mol Cancer 2010; 9: 129.
[19]
Duda DG, Duyverman AM, Kohno M, et al. Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci USA 2010; 107(50): 21677-82.
[20]
Shahar T, Rozovski U, Hess KR, et al. Percentage of mesenchymal stem cells in high-grade glioma tumor samples correlates with patient survival. Neuro-Oncol 2017; 19(5): 660-8.
[21]
Sun B, Roh KH, Park JR, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy 2009; 11(3): 289-98. 1 p following 98.
[22]
Khakoo AY, Pati S, Anderson SA, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med 2006; 203(5): 1235-47.
[23]
Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res 2008; 18(4): 500-7.
[24]
Liu J, Han G, Liu H, Qin C. Suppression of cholangiocarcinoma cell growth by human umbilical cord mesenchymal stem cells: A possible role of Wnt and Akt signaling. Plos One 2013; 8(4): e62844.
[25]
Wu S, Ju GQ, Du T, Zhu YJ, Liu GH. Microvesicles derived from human umbilical cord wharton’s jelly mesenchymal stem cells attenuate bladder tumor cell growth In vitro and In vivo. Plos One 2013; 8(4): e61366.
[26]
Otsu K, Das S, Houser SD, Quadri SK, Bhattacharya S, Bhattacharya J. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells. Blood 2009; 113(18): 4197-205.
[27]
Ghaderi A, Abtahi S. Mesenchymal stem cells: Miraculous healers or dormant killers? Stem Cell Rev 2018; 14(5): 722-33.
[28]
Roorda BD, Ter Elst A, Kamps WA, de Bont ES. Bone marrow-derived cells and tumor growth: Contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol 2009; 69(3): 187-98.
[29]
Studeny M, Marini FC, Dembinski JL, et al. Mesenchymal stem cells: Potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004; 96(21): 1593-603.
[30]
Dvorak HF. Tumors: Wounds that do not heal-redux. Cancer Immunol Res 2015; 3(1): 1-11.
[31]
Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium. Stem Cells 2009; 27(4): 857-65.
[32]
Komarova S, Roth J, Alvarez R, Curiel DT, Pereboeva L. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. J Ovarian Res 2010; 3: 12.
[33]
Kimura K, Kishida T, Wakao J, et al. Tumor-homing effect of human mesenchymal stem cells in a TH-MYCN mouse model of neuroblastoma. J Pediatr Surg 2016; 51(12): 2068-73.
[34]
Pacioni S, D’Alessandris QG, Giannetti S, et al. Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts. Stem Cell Res Ther 2017; 8(1): 53.
[35]
Kim R, Park SI, Lee CY, et al. Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and -218. Mol Cell Biochem 2017; 427(1-2): 177-85.
[36]
Orciani M, Davis S, Appolloni G, et al. Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 2015; 22(1): 9-16.
[37]
Hu J, Zhou Z, Shi S, et al. Mesenchymal stem-like cells isolated from human esophageal carcinoma and adjacent non-cancerous tissues. Oncol Lett 2013; 5(1): 179-84.
[38]
Zhang C, Zhai W, Xie Y, Chen Q, Zhu W, Sun X. Mesenchymal stem cells derived from breast cancer tissue promote the proliferation and migration of the MCF-7 cell line in vitro. Oncol Lett 2013; 6(6): 1577-82.
[39]
Lazennec G, Lam PY. Recent discoveries concerning the tumor - mesenchymal stem cell interactions. Biochim Biophys Acta 2016; 1866(2): 290-9.
[40]
Rhee KJ, Lee JI, Eom YW. Mesenchymal stem cell-mediated effects of tumor support or suppression. Int J Mol Sci 2015; 16(12): 30015-33.
[41]
Alkatout I, Hubner F, Wenners A, et al. In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer. Exp Mol Pathol 2017; 102(2): 268-75.
[42]
Jing Y, Han Z, Zhang S, Liu Y, Wei L. Epithelial-Mesenchymal Transition in tumor microenvironment. Cell Biosci 2011; 1: 29.
[43]
Jung HY, Fattet L, Yang J. Molecular pathways: Linking tumor microenvironment to epithelial-mesenchymal transition in metastasis. Clin Cancer Res 2015; 21(5): 962-8.
[44]
Wang Y, Chen X, Cao W, Shi Y. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol 2014; 15(11): 1009-16.
[45]
Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: A potential therapeutic strategy for type 1 diabetes. Diabetes 2008; 57(7): 1759-67.
[46]
Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: Immune evasive, not immune privileged. Nat Biotechnol 2014; 32(3): 252-60.
[47]
Chang AI, Schwertschkow AH, Nolta JA, Wu J. Involvement of mesenchymal stem cells in cancer progression and metastases. Curr Cancer Drug Targets 2015; 15(2): 88-98.
[48]
McLean K, Gong Y, Choi Y, et al. Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest 2011; 121(8): 3206-19.
[49]
Ding DC, Liu HW, Chu TY. Interleukin-6 from ovarian mesenchymal stem cells promotes proliferation, sphere and colony formation and tumorigenesis of an ovarian cancer cell line SKOV3. J Cancer 2016; 7(13): 1815-23.
[50]
Hossain A, Gumin J, Gao F, et al. Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells 2015; 33(8): 2400-15.
[51]
Li HJ, Reinhardt F, Herschman HR, Weinberg RA. Cancer-stimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling. Cancer Discov 2012; 2(9): 840-55.
[52]
Luo J, Ok Lee S, Liang L, Huang CK, Li L, Wen S, et al. Infiltrating bone marrow mesenchymal stem cells increase prostate cancer stem cell population and metastatic ability via secreting cytokines to suppress androgen receptor signaling. Oncogene 2014; 33(21): 2768-78.
[53]
Liu S, Ginestier C, Ou SJ, et al. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res 2011; 71(2): 614-24.
[54]
Tsai KS, Yang SH, Lei YP, et al. Mesenchymal stem cells promote formation of colorectal tumors in mice. Gastroenterology 2011; 141(3): 1046-56.
[55]
Cheng P, Wang J, Waghmare I, et al. FOXD1-ALDH1A3 signaling is a determinant for the self-renewal and tumorigenicity of mesenchymal glioma stem cells. Cancer Res 2016; 76(24): 7219-30.
[56]
Cuiffo BG, Campagne A, Bell GW, et al. MSC-regulated microRNAs converge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell 2014; 15(6): 762-74.
[57]
Coffman LG, Choi YJ, McLean K, Allen BL, di Magliano MP, Buckanovich RJ. Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop. Oncotarget 2016; 7(6): 6916-32.
[58]
Gabashvili AN, Baklaushev VP, Grinenko NF, et al. Antitumor activity of rat mesenchymal stem cells during direct or indirect co-culturing with C6 glioma cells. Bull Exp Biol Med 2016; 160(4): 519-24.
[59]
Xue JG, Zhu Y, Sun ZX, et al. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness. Bmc Cancer 2015; 15.
[60]
Papaccio F, Paino F, Regad T, Papaccio G, Desiderio V, Tirino V. Concise review: Cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med 2017; 6(12): 2115-25.
[61]
Berniakovich I, Giorgio M. Low oxygen tension maintains multipotency, whereas normoxia increases differentiation of mouse bone marrow stromal cells. Int J Mol Sci 2013; 14(1): 2119-34.
[62]
Karsy M, Guan J, Jensen R, Huang LE, Colman H. The Impact of Hypoxia and Mesenchymal Transition on Glioblastoma Pathogenesis and Cancer Stem Cells Regulation. World Neurosurg 2016; 88: 222-36.
[63]
Sanchez C, Oskowitz A, Pochampally RR. Epigenetic reprogramming of IGF1 and leptin genes by serum deprivation in multipotential mesenchymal stromal cells. Stem Cells 2009; 27(2): 375-82.
[64]
Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med 2011; 9: 10.
[65]
Crisostomo PR, Wang Y, Markel TA, Wang M, Lahm T, Meldrum DR. Human mesenchymal stem cells stimulated by TNF-alpha, LPS, or hypoxia produce growth factors by an NF kappa B- but not JNK-dependent mechanism. Am J Physiol Cell Physiol 2008; 294(3): C675-82.
[66]
Hung SC, Pochampally RR, Hsu SC, et al. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. Plos One 2007; 2(5): e416.
[67]
Torsvik A, Bjerkvig R. Mesenchymal stem cell signaling in cancer progression. Cancer Treat Rev 2013; 39(2): 180-8.
[68]
Arina A, Idel C, Hyjek EM, Alegre ML, et al. Tumor-associated fibroblasts predominantly come from local and not circulating precursors. Proc Natl Acad Sci USA 2016; 113(27): 7551-6.
[69]
Cesselli D, Beltrami AP, Poz A, et al. Role of tumor associated fibroblasts in human liver regeneration, cirrhosis, and cancer. Int J Hepatol 2011; 2011: 120925.
[70]
Augsten M. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment. Front Oncol 2014; 4: 62.
[71]
Spaeth EL, Dembinski JL, Sasser AK, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. Plos One 2009; 4(4): e4992.
[72]
Haniffa MA, Wang XN, Holtick U, et al. Adult human fibroblasts are potent immunoregulatory cells and functionally equivalent to mesenchymal stem cells. J Immunol 2007; 179(3): 1595-604.
[73]
Paunescu V, Bojin FM, Tatu CA, et al. Tumour-associated fibroblasts and mesenchymal stem cells: More similarities than differences. J Cell Mol Med 2011; 15(3): 635-46.
[74]
Weis SM, Cheresh DA. Tumor Angiogenesis: molecular pathways and therapeutic targets. Nat Med 2011; 17(11): 1359-70.
[75]
Li GC, Zhang HW, Zhao QC, et al. Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor beta1. Oncol Lett 2016; 11(2): 1089-94.
[76]
Yazdani Y, Sharifi Rad MR, Taghipour M, Chenari N, Ghaderi A, Razmkhah M. Genistein suppression of matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF) expression in mesenchymal stem cell like cells isolated from high and low grade gliomas. Asian Pac J Cancer Prev 2016; 17(12): 5303-7.
[77]
Wang Y, Liu J, Jiang Q, et al. Human adipose-derived mesenchymal stem cell-secreted CXCL1 and CXCL8 facilitate breast tumor growth by promoting angiogenesis. Stem Cells 2017; 35(9): 2060-70.
[78]
Li W, Xu H, Qian C. c-Kit-positive adipose tissue-derived mesenchymal stem cells promote the growth and angiogenesis of breast cancer. Biomed Res Int 2017; 2017: 7407168.
[79]
Suzuki K, Sun R, Origuchi M, et al. Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Mol Med 2011; 17(7-8): 579-87.
[80]
Oswald J, Boxberger S, Jorgensen B, et al. Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 2004; 22(3): 377-84.
[81]
Gong M, Yu B, Wang J, et al. Mesenchymal stem cells release exosomes that transfer miRNAs to endothelial cells and promote angiogenesis. Oncotarget 2017; 8(28): 45200-12.
[82]
Nakaya Y, Sheng G. Epithelial to mesenchymal transition during gastrulation: An embryological view. Dev Growth Differ 2008; 50(9): 755-66.
[83]
Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7(2): 131-42.
[84]
Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: Migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer 2005; 5(9): 744-9.
[85]
Zhang Y, Weinberg RA. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Front Med 2018; 12(4): 361-73.
[86]
Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 2014; 15(3): 178-96.
[87]
Chen K, Liu Q, Tsang LL, et al. Human MSCs promotes colorectal cancer epithelial-mesenchymal transition and progression via CCL5/beta-catenin/Slug pathway. Cell Death Dis 2017; 8(5): e2819.
[88]
Takigawa H, Kitadai Y, Shinagawa K, et al. Mesenchymal stem cells induce epithelial to mesenchymal transition in colon cancer cells through direct cell-to-cell contact. Neoplasia 2017; 19(5): 429-38.
[89]
Lv C, Dai H, Sun M, Zhao H, Wu K, Zhu J, et al. Mesenchymal stem cells induce epithelial mesenchymal transition in melanoma by paracrine secretion of transforming growth factor-beta. Melanoma Res 2017; 27(2): 74-84.
[90]
Martin FT, Dwyer RM, Kelly J, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat 2010; 124(2): 317-26.
[91]
Yang XY, Li Z, Ma YT, et al. Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice. Cancer Cell Int 2014; 14(1): 93.
[92]
So KA, Min KJ, Hong JH, Lee JK. Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition. Int J Oncol 2015; 47(4): 1451-9.
[93]
Ridge SM, Sullivan FJ, Glynn SA. Mesenchymal stem cells: Key players in cancer progression. Mol Cancer 2017; 16(1): 31.
[94]
Kaundal U, Bagai U, Rakha A. Immunomodulatory plasticity of mesenchymal stem cells: a potential key to successful solid organ transplantation. J Transl Med 2018; 16(1): 31.
[95]
Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2(2): 141-50.
[96]
Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol 2012; 12(5): 383-96.
[97]
Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: Evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation. Blood 2006; 107(4): 1484-90.
[98]
Kim EJ, Kim N, Cho SG. The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation. Exp Mol Med 2013; 45: e2.
[99]
Razmkhah M, Jaberipour M, Hosseini A, Safaei A, Khalatbari B, Ghaderi A. Expression profile of IL-8 and growth factors in breast cancer cells and adipose-derived stem cells (ASCs) isolated from breast carcinoma. Cell Immunol 2010; 265(1): 80-5.
[100]
Puissant B, Barreau C, Bourin P, et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol 2005; 129(1): 118-29.
[101]
Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005; 105(7): 2821-7.
[102]
Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 2008; 26(1): 212-22.
[103]
Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99(10): 3838-43.
[104]
Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103(12): 4619-21.
[105]
Niu J, Yue W, Le-Le Z, Bin L, Hu X. Mesenchymal stem cells inhibit T cell activation by releasing TGF-beta1 from TGF-beta1/GARP complex. Oncotarget 2017; 8(59): 99784-800.
[106]
Shi Y, Du L, Lin L, Wang Y. Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets. Nat Rev Drug Discov 2017; 16(1): 35-52.
[107]
Li G, Yuan L, Ren X, Nian H, Zhang L, Han ZC, et al. The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis. Clin Exp Immunol 2013; 173(1): 28-37.
[108]
Carrion F, Nova E, Luz P, Apablaza F, Figueroa F. Opposing effect of mesenchymal stem cells on Th1 and Th17 cell polarization according to the state of CD4+ T cell activation. Immunol Lett 2011; 135(1-2): 10-6.
[109]
Luz-Crawford P, Kurte M, Bravo-Alegria J, et al. Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther 2013; 4(3): 65.
[110]
Yang H, Sun J, Li Y, Duan WM, Bi J, Qu T. Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4(+)CD25(high)CD45RA(+) regulatory T cell production and modulating cytokine secretion. Cell Immunol 2016; 302: 26-31.
[111]
Haddad R, Saldanha-Araujo F. Mechanisms of T-cell immunosuppression by mesenchymal stromal cells: what do we know so far? Biomed Res Int 2014; 2014: 216806.
[112]
Bailey SR, Nelson MH, Himes RA, Li Z, Mehrotra S, Paulos CM. Th17 cells in cancer: the ultimate identity crisis. Front Immunol 2014; 5: 276.
[113]
Razmkhah M, Jaberipour M, Erfani N, Habibagahi M, Talei AR, Ghaderi A. Adipose derived stem cells (ASCs) isolated from breast cancer tissue express IL-4, IL-10 and TGF-beta1 and upregulate expression of regulatory molecules on T cells: do they protect breast cancer cells from the immune response? Cell Immunol 2011; 266(2): 116-22.
[114]
Liotta F, Querci V, Mannelli G, et al. Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation. Br J Cancer 2015; 112(4): 745-54.
[115]
Ljujic B, Milovanovic M, Volarevic V, et al. Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice. Sci Rep 2013; 3: 2298.
[116]
Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 2003; 57(1): 11-20.
[117]
Yang HM, Sung JH, Choi YS, et al. Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression. Cytotherapy 2012; 14(1): 70-9.
[118]
Vellasamy S, Sandrasaigaran P, Vidyadaran S, Abdullah M, George E, Ramasamy R. Mesenchymal stem cells of human placenta and umbilical cord suppress T-cell proliferation at G0 phase of cell cycle. Cell Biol Int 2013; 37(3): 250-6.
[119]
Krampera M, Cosmi L, Angeli R, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006; 24(2): 386-98.
[120]
Francois M, Romieu-Mourez R, Stock-Martineau S, Boivin MN, Bramson JL, Galipeau J. Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood 2009; 114(13): 2632-8.
[121]
Chan JL, Tang KC, Patel AP, et al. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 2006; 107(12): 4817-24.
[122]
Zhang B, Yeo RWY, Lai RC, Sim EWK, Chin KC, Lim SK. Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway. Cytotherapy 2018; 20(5): 687-96.
[123]
Ma OK, Chan KH. Immunomodulation by mesenchymal stem cells: Interplay between mesenchymal stem cells and regulatory lymphocytes. World J Stem Cells 2016; 8(9): 268-78.
[124]
Maccario R, Podesta M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90(4): 516-25.
[125]
Di Ianni M, Del Papa B, De Ioanni M, Moretti L, Bonifacio E, Cecchini D, et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 2008; 36(3): 309-18.
[126]
Ding DC, Chou HL, Chang YH, Hung WT, Liu HW, Chu TY. Characterization of HLA-G and Related Immunosuppressive Effects in Human Umbilical Cord Stroma-Derived Stem Cells. Cell Transplant 2016; 25(2): 217-28.
[127]
Amarnath S, Foley JE, Farthing DE, et al. Bone marrow-derived mesenchymal stromal cells harness purinergenic signaling to tolerize human Th1 cells in vivo. Stem Cells 2015; 33(4): 1200-12.
[128]
Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T Cells: Role of mesenchymal stem cell-derived TGF-beta. J Immunol 2010; 184(10): 5885-94.
[129]
Lee HY, Hong IS. Double-edged sword of mesenchymal stem cells: Cancer-promoting versus therapeutic potential. Cancer Sci 2017; 108(10): 1939-46.
[130]
Wolf D, Sopper S, Pircher A, Gastl G, Wolf AM. Treg(s) in Cancer: Friends or Foe? J Cell Physiol 2015; 230(11): 2598-605.
[131]
Tang RJ, Shen SN, Zhao XY, et al. Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer. Stem Cell Res Ther 2015; 6: 71.
[132]
Tabera S, Perez-Simon JA, Diez-Campelo M, et al. The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes. Haematologica 2008; 93(9): 1301-9.
[133]
Fan L, Hu C, Chen J, Cen P, Wang J, Li L. Interaction between mesenchymal stem cells and B-Cells. Int J Mol Sci 2016; 17(5): E650.
[134]
Comoli P, Ginevri F, Maccario R, et al. Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. Nephrol Dial Transplant 2008; 23(4): 1196-202.
[135]
Asari S, Itakura S, Ferreri K, et al. Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol 2009; 37(5): 604-15.
[136]
Rasmusson I, Le Blanc K, Sundberg B, Ringden O. Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand J Immunol 2007; 65(4): 336-43.
[137]
Franquesa M, Hoogduijn MJ, Bestard O, Grinyo JM. Immunomodulatory effect of mesenchymal stem cells on B cells. Front Immunol 2012; 3: 212.
[138]
Su T, Li JK, Meng MM, et al. Bone marrow stromal cells induced activation of nuclear factor kappa B signaling protects non-Hodgkin’s B lymphoma cells from apoptosis. Tumour Biol 2016; 37(8): 10745-52.
[139]
Zitvogel L, Kroemer G. Cancer: Antibodies regulate antitumour immunity. Nature 2015; 521(7550): 35-7.
[140]
Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8(9): 726-36.
[141]
Ungerer C, Quade-Lyssy P, Radeke HH, et al. Galectin-9 Is a Suppressor of T and B Cells and Predicts the Immune Modulatory Potential of Mesenchymal Stromal Cell Preparations. Stem Cells Dev 2014; 23(7): 755-66.
[142]
Luk F, Carreras-Planella L, Korevaar SS, et al. Inflammatory conditions dictate the effect of mesenchymal stem or stromal cells on B Cell function. Front Immunol 2017; 8: 1042.
[143]
Ji YR, Yang ZX, Han ZB, et al. Mesenchymal stem cells support proliferation and terminal differentiation of B cells. Cell Physiol Biochem 2012; 30(6): 1526-37.
[144]
Liu WH, Liu JJ, Wu J, et al. Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin-10 and the JAK1/STAT3 signaling pathway. Plos One 2013; 8(1): e55487.
[145]
Chiesa S, Morbelli S, Morando S, et al. Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells. Proc Natl Acad Sci USA 2011; 108(42): 17384-9.
[146]
Tran Janco JM, Lamichhane P, Karyampudi L, Knutson KL. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol 2015; 194(7): 2985-91.
[147]
Zhang W, Ge W, Li C, et al. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 2004; 13(3): 263-71.
[148]
Zhang Y, Ge XH, Guo XJ, et al. Bone marrow mesenchymal stem cells inhibit the function of dendritic cells by secreting galectin-1. BioMed Res Int 2017; 2017: 3248605.
[149]
Spaggiari GM, Abdelrazik H, Becchetti F, Moretta L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood 2009; 113(26): 6576-83.
[150]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105(4): 1815-22.
[151]
Ghosh T, Barik S, Bhuniya A, et al. Tumor-associated mesenchymal stem cells inhibit naive T cell expansion by blocking cysteine export from dendritic cells. Int J Cancer 2016; 139(9): 2068-81.
[152]
Zhao ZG, Xu W, Sun L, Li WM, Li QB, Zou P. The characteristics and immunoregulatory functions of regulatory dendritic cells induced by mesenchymal stem cells derived from bone marrow of patient with chronic myeloid leukaemia. Eur J Cancer 2012; 48(12): 1884-95.
[153]
Bahrami B, Hosseini A, Talei AR, Ghaderi A, Razmkhah M. Adipose Derived Stem Cells Exert Immunomodulatory Effects on Natural Killer Cells in Breast Cancer. Cell J 2017; 19(1): 137-45.
[154]
Galland S, Vuille J, Martin P, et al. Tumor-derived mesenchymal stem cells use distinct mechanisms to block the activity of natural killer cell subsets. Cell Reports 2017; 20(12): 2891-905.
[155]
Spaggiari GM, Abdelrazik H, Becchetti F, Mingari MC, Moretta L. Mesenchymal stem cells inhibit natural killer cell proliferation, cytotoxicity and cytokine production: Role of indoleamine 2,3- dioxygenase and prostaglandin E2. Clin Immunol 2009; 131: S47-.
[156]
Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: Role of mesenchymal stem cell-derived TGF-beta. J Immunol 2010; 184(10): 5885-94.
[157]
Petri RM, Hackel A, Hahnel K, et al. Activated Tissue-Resident Mesenchymal Stromal Cells Regulate Natural Killer Cell Immune and Tissue-Regenerative Function. Stem Cell Rep 2017; 9(3): 985-98.
[158]
Najar M, Fayyad-Kazan M, Meuleman N, Bron D, Fayyad-Kazan H, Lagneaux L. Mesenchymal stromal cells of the bone marrow and natural killer cells: Cell interactions and cross modulation. J Cell Commun Signal 2018; 12(4): 673-88.
[159]
Cho DI, Kim MR, Jeong HY, et al. Mesenchymal stem cells reciprocally regulate the M1/M2 balance in mouse bone marrow-derived macrophages. Exp Mol Med 2014; 46: e70.
[160]
Vasandan AB, Jahnavi S, Shashank C, Prasad P, Kumar A, Prasanna SJ. Human Mesenchymal stem cells program macrophage plasticity by altering their metabolic status via a PGE2-dependent mechanism. Sci Rep 2016; 6: 38308.
[161]
Guillen MI, Platas J, Perez Del Caz MD, Mirabet V, Alcaraz MJ. Paracrine anti-inflammatory effects of adipose tissue-derived mesenchymal stem cells in human monocytes. Front Physiol 2018; 9: 661.
[162]
Mathew E, Brannon AL, Del Vecchio A, et al. Mesenchymal Stem Cells Promote Pancreatic Tumor Growth by Inducing Alternative Polarization of Macrophages. Neoplasia 2016; 18(3): 142-51.
[163]
Wolfe AR, Trenton NJ, Debeb BG, et al. Mesenchymal stem cells and macrophages interact through IL-6 to promote inflammatory breast cancer in pre-clinical models. Oncotarget 2016; 7(50): 82482-92.
[164]
Bernardo ME, Fibbe WE. Mesenchymal stromal cells: Sensors and switchers of inflammation. Cell Stem Cell 2013; 13(4): 392-402.
[165]
Melief SM, Zwaginga JJ, Fibbe WE, Roelofs H. Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cell Transl Med 2013; 2(6): 455-63.
[166]
Cassatella MA, Mosna F, Micheletti A, et al. Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells 2011; 29(6): 1001-11.
[167]
Raffaghello L, Bianchi G, Bertolotto M, et al. Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem Cells 2008; 26(1): 151-62.
[168]
Magana-Guerrero FS, Dominguez-Lopez A, Martinez-Aboytes P, Buentello-Volante B, Garfias Y. Human amniotic membrane mesenchymal stem cells inhibit neutrophil extracellular traps through TSG-6. Sci Rep 2017; 7(1): 12426.
[169]
Yu PF, Huang Y, Han YY, et al. TNFalpha-activated mesenchymal stromal cells promote breast cancer metastasis by recruiting CXCR2(+) neutrophils. Oncogene 2017; 36(4): 482-90.
[170]
Zhu Q, Zhang X, Zhang L, et al. The IL-6-STAT3 axis mediates a reciprocal crosstalk between cancer-derived mesenchymal stem cells and neutrophils to synergistically prompt gastric cancer progression. Cell Death Dis 2014; 5: e1295.
[171]
Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol 2009; 4: 127-50.


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VOLUME: 14
ISSUE: 1
Year: 2019
Page: [43 - 51]
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DOI: 10.2174/1574888X13666180816114809
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