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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

The Role of Mesenchymal Stem Cells in Cancer Immunotherapy

Author(s): Yueshui Zhao, Xianmei Zhong, Fukuan Du, Xu Wu, Mingxing Li, Qinglian Wen, Jing Shen, Yu Chen, Xinyi Zhang, Zhongming Yang, Ying Deng, Xiang Liu, Chang Zou*, Yu Du* and Zhangang Xiao*

Volume 18, Issue 8, 2023

Published on: 23 January, 2023

Page: [1056 - 1068] Pages: 13

DOI: 10.2174/1574888X18666230103120302

Price: $65

Open Access Journals Promotions 2
Abstract

Mesenchymal stem cells (MSCs) are getting attention in the field of cancer immunotherapy. The main effects of MSCs on tumors are homing and regulation of inflammatory and immune responses. Indeed, cancer immunotherapy has become a promising treatment and MSCs play a potential role in regulating the efficacy of immunotherapy. In addition, MSCs are an ideal carrier for immunomodulatory protein transmission. As such MSCs combined with immunotherapy drugs could act synergistically against tumors, throwing a great impact on cancer therapy. And MSCs may have potential in the treatment of cytokine storm or cytokine release syndrome (CRS). It is assumed that MSCs can form chimeric antigen receptor MSCs (CAR-MSCs). Whether CAR-MSCs can provide a new idea of cancer immunotherapy is unknown. It is a prime time to review the latest progress of MSCs in cancer immunotherapy, in order to clarify to fully understand the role of MSCs in cancer therapy in clinical practice.

Keywords: Mesenchymal stem cells, tumor, cancer immunotherapy, cytokine storm, chimeric antigen receptor, cellular immune cell therapy (CAR-T).

Graphical Abstract
[1]
Porada C, Zanjani E, Almeida-Porada G. Adult mesenchymal stem cells: A pluripotent population with multiple applications. Curr Stem Cell Res Ther 2006; 1(3): 365-9.
[http://dx.doi.org/10.2174/157488806778226821] [PMID: 18220880]
[2]
Simões BP, Tone LG, Zago MA, Figueiredo MS. Splenic function in acute leukemia. Acta Haematol 1995; 94(3): 123-7.
[http://dx.doi.org/10.1159/000203993] [PMID: 7502627]
[3]
Kennedy LB, Salama AKS. A review of cancer immunotherapy toxicity. CA Cancer J Clin 2020; 70(2): 86-104.
[http://dx.doi.org/10.3322/caac.21596] [PMID: 31944278]
[4]
Meng MY, Li L, Wang WJ, et al. Assessment of tumor promoting effects of amniotic and umbilical cord mesenchymal stem cells in vitro and in vivo. J Cancer Res Clin Oncol 2019; 145(5): 1133-46.
[http://dx.doi.org/10.1007/s00432-019-02859-6] [PMID: 30805774]
[5]
Li A, Guo F, Pan Q, et al. Mesenchymal stem cell therapy: Hope for patients with systemic lupus erythematosus. Front Immunol 2021; 12: 728190.
[http://dx.doi.org/10.3389/fimmu.2021.728190] [PMID: 34659214]
[6]
Murata M, Teshima T. Treatment of steroid-refractory acute graft-versus-host disease using commercial mesenchymal stem cell products. Front Immunol 2021; 12: 724380.
[http://dx.doi.org/10.3389/fimmu.2021.724380] [PMID: 34489977]
[7]
Mohr A, Zwacka R. The future of mesenchymal stem cell-based therapeutic approaches for cancer – From cells to ghosts. Cancer Lett 2018; 414: 239-49.
[http://dx.doi.org/10.1016/j.canlet.2017.11.025] [PMID: 29175461]
[8]
Tomita M, Maeda M, Maezawa H, Usami N, Kobayashi K. Bystander cell killing in normal human fibroblasts is induced by synchrotron X-ray microbeams. Radiat Res 2010; 173(3): 380-5.
[http://dx.doi.org/10.1667/RR1995.1] [PMID: 20199223]
[9]
Oun R, Moussa Y, Wheate N. The side effects of platinum-based chemotherapy drugs: A review for chemists. Dalton Trans 2018; 47(19): 6645-53.
[10]
Mohammadi M, Jaafari MR, Mirzaei HR, Mirzaei H. Mesenchymal stem cell: A new horizon in cancer gene therapy. Cancer Gene Ther 2016; 23(9): 285-6.
[http://dx.doi.org/10.1038/cgt.2016.35] [PMID: 27650780]
[11]
Motegi S, Ishikawa O. Mesenchymal stem cells: The roles and functions in cutaneous wound healing and tumor growth. J Dermatol Sci 2017; 86(2): 83-9.
[http://dx.doi.org/10.1016/j.jdermsci.2016.11.005] [PMID: 27866791]
[12]
Hagenhoff A, Bruns CJ, Zhao Y, et al. Harnessing mesenchymal stem cell homing as an anticancer therapy. Expert Opin Biol Ther 2016; 16(9): 1079-92.
[http://dx.doi.org/10.1080/14712598.2016.1196179] [PMID: 27270211]
[13]
Al-kharboosh R, ReFaey K, Lara-Velazquez M, Grewal SS, Imitola J, Quiñones-Hinojosa A. Inflammatory mediators in glioma microenvironment play a dual role in gliomagenesis and mesenchymal stem cell homing: Implication for cellular therapy. Mayo Clin Proc Innov Qual Outcomes 2020; 4(4): 443-59.
[http://dx.doi.org/10.1016/j.mayocpiqo.2020.04.006] [PMID: 32793872]
[14]
Mirzaei H, Sahebkar A, Avan A, et al. Application of mesenchymal stem cells in melanoma: A potential therapeutic strategy for delivery of targeted agents. Curr Med Chem 2016; 23(5): 455-63.
[http://dx.doi.org/10.2174/0929867323666151217122033] [PMID: 26674785]
[15]
Li M, Zeng L, Liu S, et al. Transforming growth factor-β promotes homing and therapeutic efficacy of human mesenchymal stem cells to glioblastoma. J Neuropathol Exp Neurol 2019; 78(4): 315-25.
[http://dx.doi.org/10.1093/jnen/nlz016] [PMID: 30863846]
[16]
Naderi-Meshkin H, Bahrami AR, Bidkhori HR, Mirahmadi M, Ahmadiankia N. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy. Cell Biol Int 2015; 39(1): 23-34.
[http://dx.doi.org/10.1002/cbin.10378] [PMID: 25231104]
[17]
Karp JM, Leng Teo GS. Mesenchymal stem cell homing: The devil is in the details. Cell Stem Cell 2009; 4(3): 206-16.
[http://dx.doi.org/10.1016/j.stem.2009.02.001] [PMID: 19265660]
[18]
Liu Y, Cao X. Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med 2016; 94(5): 509-22.
[http://dx.doi.org/10.1007/s00109-015-1376-x] [PMID: 26689709]
[19]
Castro-Manrreza ME. Participation of mesenchymal stem cells in the regulation of immune response and cancer development. Bol Méd Hosp Infant México 2016; 73(6): 380-7.
[http://dx.doi.org/10.1016/j.bmhimx.2016.10.003] [PMID: 29421282]
[20]
Chae HK, Song WJ, Ahn JO, et al. Immunomodulatory effects of soluble factors secreted by feline adipose tissue-derived mesenchymal stem cells. Vet Immunol Immunopathol 2017; 191: 22-9.
[http://dx.doi.org/10.1016/j.vetimm.2017.07.013] [PMID: 28895862]
[21]
Galland S, Stamenkovic I. Mesenchymal stromal cells in cancer: A review of their immunomodulatory functions and dual effects on tumor progression. J Pathol 2020; 250(5): 555-72.
[http://dx.doi.org/10.1002/path.5357] [PMID: 31608444]
[22]
Song Y, Lim JY, Lim T, et al. Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms. World J Stem Cells 2020; 12(9): 1032-49.
[http://dx.doi.org/10.4252/wjsc.v12.i9.1032] [PMID: 33033563]
[23]
Uccelli A, Pistoia V, Moretta L. Mesenchymal stem cells: A new strategy for immunosuppression? Trends Immunol 2007; 28(5): 219-26.
[http://dx.doi.org/10.1016/j.it.2007.03.001] [PMID: 17400510]
[24]
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): 650.
[http://dx.doi.org/10.3390/ijms17050650] [PMID: 27164080]
[25]
Moloudizargari M, Govahi A, Fallah M, Rezvanfar MA, Asghari MH, Abdollahi M. The mechanisms of cellular crosstalk between mesenchymal stem cells and natural killer cells: Therapeutic implications. J Cell Physiol 2021; 236(4): 2413-29.
[http://dx.doi.org/10.1002/jcp.30038] [PMID: 32892356]
[26]
Ðokić JM, Tomić SZ, Čolić MJ. Cross-talk between mesenchymal stem/stromal cells and dendritic cells. Curr Stem Cell Res Ther 2016; 11(1): 51-65.
[http://dx.doi.org/10.2174/1574888X10666150904114035] [PMID: 26337378]
[27]
Luque-Campos N, Bustamante-Barrientos FA, Pradenas C, et al. The macrophage response is driven by mesenchymal stem cell-mediated metabolic reprogramming. Front Immunol 2021; 12: 624746.
[http://dx.doi.org/10.3389/fimmu.2021.624746] [PMID: 34149687]
[28]
Deng Y, Zhang Y, Ye L, et al. Umbilical cord-derived mesenchymal stem cells instruct monocytes towards an IL10-producing phenotype by secreting IL6 and HGF. Sci Rep 2016; 6(1): 37566.
[http://dx.doi.org/10.1038/srep37566] [PMID: 27917866]
[29]
Harrell CR, Djonov V, Volarevic V. The cross-talk between mesenchymal stem cells and immune cells in tissue repair and regeneration. Int J Mol Sci 2021; 22(5): 2472.
[http://dx.doi.org/10.3390/ijms22052472] [PMID: 33804369]
[30]
Li W, Ren G, Huang Y, et al. Mesenchymal stem cells: A double-edged sword in regulating immune responses. Cell Death Differ 2012; 19(9): 1505-13.
[http://dx.doi.org/10.1038/cdd.2012.26] [PMID: 22421969]
[31]
Court AC, Le-Gatt A, Luz-Crawford P, et al. Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response. EMBO Rep 2020; 21(2): e48052.
[http://dx.doi.org/10.15252/embr.201948052] [PMID: 31984629]
[32]
Luz-Crawford P, Hernandez J, Djouad F, et al. Mesenchymal stem cell repression of Th17 cells is triggered by mitochondrial transfer. Stem Cell Res Ther 2019; 10(1): 232.
[http://dx.doi.org/10.1186/s13287-019-1307-9] [PMID: 31370879]
[33]
Do J, Zwick D, Kenyon JD, et al. Mesenchymal stromal cell mitochondrial transfer to human induced T-regulatory cells mediates FOXP3 stability. Sci Rep 2021; 11(1): 10676.
[http://dx.doi.org/10.1038/s41598-021-90115-8] [PMID: 34021231]
[34]
Li P, Gong Z, Shultz LD, Ren G. Mesenchymal stem cells: From regeneration to cancer. Pharmacol Ther 2019; 200: 42-54.
[http://dx.doi.org/10.1016/j.pharmthera.2019.04.005] [PMID: 30998940]
[35]
Bajetto A, Pattarozzi A, Corsaro A, et al. Different effects of human umbilical cord mesenchymal stem cells on glioblastoma stem cells by direct cell interaction or via released soluble factors. Front Cell Neurosci 2017; 11: 312.
[http://dx.doi.org/10.3389/fncel.2017.00312] [PMID: 29081734]
[36]
Yan L, Zheng D, Xu RH. Critical role of tumor necrosis factor signaling in mesenchymal stem cell-based therapy for autoimmune and inflammatory diseases. Front Immunol 2018; 9: 1658.
[http://dx.doi.org/10.3389/fimmu.2018.01658] [PMID: 30079066]
[37]
Razazian M, Khosravi M, Bahiraii S, Uzan G, Shamdani S, Naserian S. Differences and similarities between mesenchymal stem cell and endothelial progenitor cell immunoregulatory properties against T cells. World J Stem Cells 2021; 13(8): 971-84.
[http://dx.doi.org/10.4252/wjsc.v13.i8.971] [PMID: 34567420]
[38]
Trivanović D, Krstić J, Djordjević IO, et al. The roles of mesenchymal stromal/stem cells in tumor microenvironment associated with inflammation. Mediators Inflamm 2016; 2016: 1-14.
[http://dx.doi.org/10.1155/2016/7314016] [PMID: 27630452]
[39]
Chen J, Ji T, Wu D, et al. Human mesenchymal stem cells promote tumor growth via MAPK pathway and metastasis by epithelial mesenchymal transition and integrin α5 in hepatocellular carcinoma. Cell Death Dis 2019; 10(6): 425.
[http://dx.doi.org/10.1038/s41419-019-1622-1] [PMID: 31142737]
[40]
Liu QW, Li JY, Zhang XC, et al. Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour‐bearing mice. J Cell Mol Med 2020; 24(18): 10525-41.
[http://dx.doi.org/10.1111/jcmm.15668] [PMID: 32798252]
[41]
Nasuno M, Arimura Y, Nagaishi K, et al. Mesenchymal stem cells cancel azoxymethane-induced tumor initiation. Stem Cells 2014; 32(4): 913-25.
[http://dx.doi.org/10.1002/stem.1594] [PMID: 24715689]
[42]
Einem JC, Guenther C, Volk HD, et al. Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial. Int J Cancer 2019; 145(6): 1538-46.
[http://dx.doi.org/10.1002/ijc.32230] [PMID: 30801698]
[43]
Lee M, Jeong SY, Ha J, et al. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo. Biochem Biophys Res Commun 2014; 446(4): 983-9.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.051] [PMID: 24657442]
[44]
Ridge SM, Sullivan FJ, Glynn SA. Mesenchymal stem cells: Key players in cancer progression. Mol Cancer 2017; 16(1): 31.
[http://dx.doi.org/10.1186/s12943-017-0597-8] [PMID: 28148268]
[45]
Weinstock A, Pevsner-Fischer M, Porat Z, Selitrennik M, Zipori D. Cultured mesenchymal stem cells stimulate an immune response by providing immune cells with toll-like receptor 2 ligand. Stem Cell Rev 2015; 11(6): 826-40.
[http://dx.doi.org/10.1007/s12015-015-9614-8] [PMID: 26250539]
[46]
Mao J, Cao M, Zhang F, et al. Peritumoral administration of IFNβ upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model. J Immunother Cancer 2020; 8(1): e000164.
[http://dx.doi.org/10.1136/jitc-2019-000164] [PMID: 32169868]
[47]
Du L, Liang Q, Ge S, Yang C, Yang P. The growth inhibitory effect of human gingiva-derived mesenchymal stromal cells expressing interferon-β on tongue squamous cell carcinoma cells and xenograft model. Stem Cell Res Ther 2019; 10(1): 224.
[http://dx.doi.org/10.1186/s13287-019-1320-z] [PMID: 31358054]
[48]
Ren C, Kumar S, Chanda D, et al. Cancer gene therapy using mesenchymal stem cells expressing interferon-β in a mouse prostate cancer lung metastasis model. Gene Ther 2008; 15(21): 1446-53.
[http://dx.doi.org/10.1038/gt.2008.101] [PMID: 18596829]
[49]
Shen CJ, Chan TF, Chen CC, Hsu YC, Long CY, Lai CS. Human umbilical cord matrix-derived stem cells expressing interferon-β gene inhibit breast cancer cells via apoptosis. Oncotarget 2016; 7(23): 34172-9.
[http://dx.doi.org/10.18632/oncotarget.8997] [PMID: 27129156]
[50]
Lee MW, Ryu S, Kim DS, et al. Mesenchymal stem cells in suppression or progression of hematologic malignancy: Current status and challenges. Leukemia 2019; 33(3): 597-611.
[http://dx.doi.org/10.1038/s41375-018-0373-9] [PMID: 30705410]
[51]
Yang X, Du J, Xu X, Xu C, Song W. IFN-γ-secreting-mesenchymal stem cells exert an antitumor effect in vivo via the trail pathway. J Immunol Res 2014; 2014: 318098.
[http://dx.doi.org/10.1155/2014/318098] [PMID: 24971369]
[52]
Li X, Lu Y, Huang W, et al. In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia. Hematol Oncol 2006; 24(3): 151-8.
[http://dx.doi.org/10.1002/hon.779] [PMID: 16700092]
[53]
Lazear HM, Schoggins JW, Diamond MS. Shared and distinct functions of type I and type III interferons. Immunity 2019; 50(4): 907-23.
[http://dx.doi.org/10.1016/j.immuni.2019.03.025] [PMID: 30995506]
[54]
Müller L, Aigner P, Stoiber D, Type I. Type I interferons and natural killer cell regulation in cancer. Front Immunol 2017; 8: 304.
[http://dx.doi.org/10.3389/fimmu.2017.00304] [PMID: 28408907]
[55]
Bahrambeigi V, Ahmadi N, Moisyadi S, Urschitz J, Salehi R, Haghjooy Javanmard S. PhiC31/PiggyBac modified stromal stem cells: Effect of interferon γ and/or tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on murine melanoma. Mol Cancer 2014; 13(1): 255.
[http://dx.doi.org/10.1186/1476-4598-13-255] [PMID: 25428727]
[56]
Anestakis D, Petanidis S, Kalyvas S, et al. Mechanisms and applications of interleukins in cancer immunotherapy. Int J Mol Sci 2015; 16(1): 1691-710.
[http://dx.doi.org/10.3390/ijms16011691] [PMID: 25590298]
[57]
Setrerrahmane S, Xu H. Tumor-related interleukins: Old validated targets for new anti-cancer drug development. Mol Cancer 2017; 16(1): 153.
[http://dx.doi.org/10.1186/s12943-017-0721-9] [PMID: 28927416]
[58]
Dhupkar P, Gordon N. Interleukin-2: Old and new approaches to enhance immune-therapeutic efficacy. Adv Exp Med Biol 2017; 995: 33-51.
[http://dx.doi.org/10.1007/978-3-319-53156-4_2] [PMID: 28321811]
[59]
Zhou J, Liang T, Wang D, et al. IFN α -expressing amniotic fluid-derived mesenchymal stem cells migrate to and suppress HeLa cell-derived tumors in a mouse model. Stem Cells Int 2018; 2018: 1241323.
[http://dx.doi.org/10.1155/2018/1241323] [PMID: 29760719]
[60]
Shou P, Chen Q, Jiang J, et al. Type I interferons exert anti-tumor effect via reversing immunosuppression mediated by mesenchymal stromal cells. Oncogene 2016; 35(46): 5953-62.
[http://dx.doi.org/10.1038/onc.2016.128] [PMID: 27109100]
[61]
Chen X, Wang K, Chen S, Chen Y. Effects of mesenchymal stem cells harboring the Interferon-β gene on A549 lung cancer in nude mice. Pathol Res Pract 2019; 215(3): 586-93.
[http://dx.doi.org/10.1016/j.prp.2019.01.013] [PMID: 30683475]
[62]
Chulpanova DS, Solovyeva VV, James V, et al. Human mesenchymal stem cells overexpressing interleukin 2 can suppress proliferation of neuroblastoma cells in co-culture and activate mononuclear cells in vitro. Bioengineering 2020; 7(2): 59.
[http://dx.doi.org/10.3390/bioengineering7020059] [PMID: 32560387]
[63]
You Q, Yao Y, Zhang Y, Fu S, Du M, Zhang G. Effect of targeted ovarian cancer therapy using amniotic fluid mesenchymal stem cells transfected with enhanced green fluorescent protein-human interleukin-2 in vivo. Mol Med Rep 2015; 12(4): 4859-66.
[http://dx.doi.org/10.3892/mmr.2015.4076] [PMID: 26179662]
[64]
Zhao C, Pu Y, Zhang H, et al. IL10-modified human mesenchymal stem cells inhibit pancreatic cancer growth through angiogenesis inhibition. J Cancer 2020; 11(18): 5345-52.
[http://dx.doi.org/10.7150/jca.38062] [PMID: 32742480]
[65]
Wang H, Wang J, Shi X, Ding Y. Genetically engineered bone marrow-derived mesenchymal stem cells co-expressing IFN-γ and IL-10 inhibit hepatocellular carcinoma by modulating MAPK pathway. J Buon 2017; 22(6): 1517-24.
[66]
Li X, Zhang P, Liu X, Lv P. Expression of interleukin-12 by adipose-derived mesenchymal stem cells for treatment of lung adenocarcinoma. Thorac Cancer 2015; 6(1): 80-4.
[http://dx.doi.org/10.1111/1759-7714.12151] [PMID: 26273339]
[67]
Elzaouk L, Moelling K, Pavlovic J. Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model. Exp Dermatol 2006; 15(11): 865-74.
[http://dx.doi.org/10.1111/j.1600-0625.2006.00479.x] [PMID: 17002683]
[68]
Jeong KY, Lee EJ, Kim SJ, Yang SH, Sung YC, Seong J. Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma. Int J Cancer 2015; 137(3): 721-30.
[http://dx.doi.org/10.1002/ijc.29428] [PMID: 25639194]
[69]
Wang A, Zhou X, Zhao J, Liu T, Xu J. Therapeutic effects of bone marrow mesenchymal stem cells expressing interleukin-12 in mice bearing malignant ascites tumor. Int J Clin Exp Med 2015; 8(9): 15840-5.
[PMID: 26629085]
[70]
Ryu CH, Park SH, Park SA, et al. Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells. Hum Gene Ther 2011; 22(6): 733-43.
[http://dx.doi.org/10.1089/hum.2010.187] [PMID: 21261460]
[71]
Duan X, Guan H, Cao Y, Kleinerman ES. Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors. Cancer 2009; 115(1): 13-22.
[http://dx.doi.org/10.1002/cncr.24013] [PMID: 19051291]
[72]
Jing W, Chen Y, Lu L, et al. Human umbilical cord blood-derived mesenchymal stem cells producing IL15 eradicate established pancreatic tumor in syngeneic mice. Mol Cancer Ther 2014; 13(8): 2127-37.
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0175] [PMID: 24928851]
[73]
Liu X, Hu J, Li Y, et al. Mesenchymal stem cells expressing interleukin-18 inhibit breast cancer in a mouse model. Oncol Lett 2018; 15(5): 6265-74.
[http://dx.doi.org/10.3892/ol.2018.8166] [PMID: 29725393]
[74]
Xu G, Jiang XD, Xu Y, et al. Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats. Cell Biol Int 2009; 33(4): 466-74.
[http://dx.doi.org/10.1016/j.cellbi.2008.07.023] [PMID: 18725309]
[75]
Kim N, Nam YS, Im KI, et al. IL-21-expressing mesenchymal stem cells prevent lethal B-cell lymphoma through efficient delivery of IL-21, which redirects the immune system to target the tumor. Stem Cells Dev 2015; 24(23): 2808-21.
[http://dx.doi.org/10.1089/scd.2015.0103] [PMID: 26415081]
[76]
Hu W, Wang J, He X, et al. Human umbilical blood mononuclear cell-derived mesenchymal stem cells serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice. Biotechnol Appl Biochem 2011; 58(6): 397-404.
[http://dx.doi.org/10.1002/bab.63] [PMID: 22172102]
[77]
Zhang Y, Wang J, Ren M, et al. Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice. J Ovarian Res 2014; 7(1): 8.
[http://dx.doi.org/10.1186/1757-2215-7-8] [PMID: 24444073]
[78]
Zhang Y, Wang J, Wu D, et al. IL-21-secreting hUCMSCs combined with miR-200c inhibit tumor growth and metastasis via repression of Wnt/β-catenin signaling and epithelial-mesenchymal transition in epithelial ovarian cancer. OncoTargets Ther 2018; 11: 2037-50.
[http://dx.doi.org/10.2147/OTT.S147855] [PMID: 29692616]
[79]
Fan S, Gao H, Ji W, et al. Umbilical cord‐derived mesenchymal stromal/stem cells expressing IL‐24 induce apoptosis in gliomas. J Cell Physiol 2020; 235(2): 1769-79.
[http://dx.doi.org/10.1002/jcp.29095] [PMID: 31301067]
[80]
Suzuki T, Kawamura K, Li Q, et al. Mesenchymal stem cells are efficiently transduced with adenoviruses bearing type 35-derived fibers and the transduced cells with the IL-28A gene produces cytotoxicity to lung carcinoma cells co-cultured. BMC Cancer 2014; 14(1): 713.
[http://dx.doi.org/10.1186/1471-2407-14-713] [PMID: 25255777]
[81]
Iida Y, Yoshikawa R, Murata A, et al. Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells. J Immunother Cancer 2020; 8(2): e000582.
[http://dx.doi.org/10.1136/jitc-2020-000582] [PMID: 32675195]
[82]
Kenarkoohi A, Bamdad T, Soleimani M, Soleimanjahi H, Fallah A, Falahi S. HSV-TK expressing mesenchymal stem cells exert inhibitory effect on cervical cancer model. Int J Mol Cell Med 2020; 9(2): 146-54.
[PMID: 32934952]
[83]
Yu Y, Zhang Q, Meng Q, et al. Mesenchymal stem cells overexpressing Sirt1 inhibit prostate cancer growth by recruiting natural killer cells and macrophages. Oncotarget 2016; 7(44): 71112-22.
[http://dx.doi.org/10.18632/oncotarget.12737] [PMID: 27764779]
[84]
Zhang Q, Yuan XF, Lu Y, et al. Surface expression of anti‐CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A‐engineered human umbilical cord mesenchymal stem cells. Int J Cancer 2017; 141(7): 1445-57.
[http://dx.doi.org/10.1002/ijc.30846] [PMID: 28643325]
[85]
Szoor A, Vaidya A, Velasquez MP, et al. T cell-activating mesenchymal stem cells as a biotherapeutic for HCC. Mol Ther Oncolytics 2017; 6: 69-79.
[http://dx.doi.org/10.1016/j.omto.2017.07.002] [PMID: 28856237]
[86]
Zhang X, Yang Y, Zhang L, et al. Mesenchymal stromal cells as vehicles of tetravalent bispecific Tandab (CD3/CD19) for the treatment of B cell lymphoma combined with IDO pathway inhibitor d-1-methyl-tryptophan. J Hematol Oncol 2017; 10(1): 56.
[http://dx.doi.org/10.1186/s13045-017-0397-z] [PMID: 28228105]
[87]
Yang Y, Zhang X, Lin F, et al. Bispecific CD3-HAC carried by E1A-engineered mesenchymal stromal cells against metastatic breast cancer by blocking PD-L1 and activating T cells. J Hematol Oncol 2019; 12(1): 46.
[http://dx.doi.org/10.1186/s13045-019-0723-8] [PMID: 31023384]
[88]
Moreno R, Fajardo CA, Farrera-Sal M, et al. Enhanced antitumor efficacy of oncolytic adenovirus–loaded menstrual blood–derived mesenchymal stem cells in combination with peripheral blood mononuclear cells. Mol Cancer Ther 2019; 18(1): 127-38.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0431] [PMID: 30322950]
[89]
Lu JH, Peng BY, Chang CC, et al. Tumor-targeted immunotherapy by using primary adipose-derived stem cells and an antigen-specific protein vaccine. Cancers 2018; 10(11): 446.
[http://dx.doi.org/10.3390/cancers10110446] [PMID: 30445793]
[90]
Wei HJ, Wu ATH, Hsu CH, et al. The development of a novel cancer immunotherapeutic platform using tumor-targeting mesenchymal stem cells and a protein vaccine. Mol Ther 2011; 19(12): 2249-57.
[http://dx.doi.org/10.1038/mt.2011.152] [PMID: 21792181]
[91]
Zeng Y, Li B, Li T, et al. CD90low MSCs modulate intratumoral immunity to confer antitumor activity in a mouse model of ovarian cancer. Oncotarget 2019; 10(43): 4479-91.
[http://dx.doi.org/10.18632/oncotarget.27065] [PMID: 31320999]
[92]
Hombach AA, Geumann U, Günther C, Hermann FG, Abken H. IL7-IL12 engineered Mesenchymal Stem Cells (MSCs) improve A CAR T cell attack against colorectal cancer cells. Cells 2020; 9(4): 873.
[http://dx.doi.org/10.3390/cells9040873] [PMID: 32260097]
[93]
Huang R, Li X, He Y, et al. Recent advances in CAR-T cell engineering. J Hematol Oncol 2020; 13(1): 86.
[http://dx.doi.org/10.1186/s13045-020-00910-5] [PMID: 32616000]
[94]
Sheth VS, Gauthier J. Taming the beast: CRS and ICANS after CAR T-cell therapy for ALL. Bone Marrow Transplant 2021; 56(3): 552-66.
[http://dx.doi.org/10.1038/s41409-020-01134-4] [PMID: 33230186]
[95]
Schubert ML, Schmitt M, Wang L, et al. Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol 2021; 32(1): 34-48.
[http://dx.doi.org/10.1016/j.annonc.2020.10.478] [PMID: 33098993]
[96]
Acharya UH, Dhawale T, Yun S, et al. Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy. Expert Rev Hematol 2019; 12(3): 195-205.
[http://dx.doi.org/10.1080/17474086.2019.1585238] [PMID: 30793644]
[97]
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer 2018; 6(1): 56.
[http://dx.doi.org/10.1186/s40425-018-0343-9] [PMID: 29907163]
[98]
Hao Z, Li R, Meng L, Han Z, Hong Z. Macrophage, the potential key mediator in CAR-T related CRS. Exp Hematol Oncol 2020; 9(1): 15.
[http://dx.doi.org/10.1186/s40164-020-00171-5] [PMID: 32665874]
[99]
Liu Y, Fang Y, Chen X, et al. Gasdermin E–mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. Sci Immunol 2020; 5(43): eaax7969.
[http://dx.doi.org/10.1126/sciimmunol.aax7969] [PMID: 31953257]
[100]
Maggini J, Mirkin G, Bognanni I, et al. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One 2010; 5(2): e9252.
[http://dx.doi.org/10.1371/journal.pone.0009252] [PMID: 20169081]
[101]
Hong R, Wang Z, Sui A, et al. Gingival mesenchymal stem cells attenuate pro-inflammatory macrophages stimulated with oxidized low-density lipoprotein and modulate lipid metabolism. Arch Oral Biol 2019; 98: 92-8.
[http://dx.doi.org/10.1016/j.archoralbio.2018.11.007] [PMID: 30468993]
[102]
Lu X, Li N, Zhao L, et al. Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype. Exp Eye Res 2020; 191: 107905.
[http://dx.doi.org/10.1016/j.exer.2019.107905] [PMID: 31891674]
[103]
Jeong WY, Kim JH, Kim CW. Co-culture of human bone marrow mesenchymal stem cells and macrophages attenuates lipopolysaccharide-induced inflammation in human corneal epithelial cells. Biosci Biotechnol Biochem 2018; 82(5): 800-9.
[http://dx.doi.org/10.1080/09168451.2018.1438167] [PMID: 29452534]
[104]
Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther 2011; 2(4): 34.
[http://dx.doi.org/10.1186/scrt75] [PMID: 21861858]
[105]
Weiss ARR, Dahlke MH. Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol 2019; 10: 1191.
[http://dx.doi.org/10.3389/fimmu.2019.01191] [PMID: 31214172]
[106]
Ghosh T, Barik S, Bhuniya A, et al. Tumor-associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells. Int J Cancer 2016; 139(9): 2068-81.
[http://dx.doi.org/10.1002/ijc.30265] [PMID: 27405489]
[107]
Zanetti SR, Romecin PA, Vinyoles M, et al. Bone marrow MSC from pediatric patients with B-ALL highly immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity. J Immunother Cancer 2020; 8(2): e001419.
[http://dx.doi.org/10.1136/jitc-2020-001419] [PMID: 32868394]
[108]
McKenna MK, Englisch A, Brenner B, et al. Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity. Mol Ther 2021; 29(5): 1808-20.
[http://dx.doi.org/10.1016/j.ymthe.2021.02.004] [PMID: 33571680]
[109]
Kaffash Farkhad N, Reihani H. sedaghat A, Moghadam AA, Moghadam AB, Tavakol-Afshari J. Are mesenchymal stem cells able to manage cytokine storm in COVID-19 patients? A review of recent studies. Regen Ther 2021; 18: 152-60.
[http://dx.doi.org/10.1016/j.reth.2021.05.007] [PMID: 34124322]
[110]
Wang L, Li Y, Xu M, et al. Regulation of inflammatory cytokine storms by mesenchymal stem cells. Front Immunol 2021; 12: 726909.
[http://dx.doi.org/10.3389/fimmu.2021.726909] [PMID: 34394132]
[111]
Song N, Wakimoto H, Rossignoli F, et al. Mesenchymal stem cell immunomodulation: In pursuit of controlling COVID-19 related cytokine storm. Stem Cells 2021; 39(6): 707-22.
[http://dx.doi.org/10.1002/stem.3354] [PMID: 33586320]
[112]
Schweizer MT, Wang H, Bivalacqua TJ, et al. A Phase I study to assess the safety and cancer-homing ability of allogeneic bone marrow-derived mesenchymal stem cells in men with localized prostate cancer. Stem Cells Transl Med 2019; 8(5): 441-9.
[http://dx.doi.org/10.1002/sctm.18-0230] [PMID: 30735000]
[113]
Ruano D, López-Martín J, Moreno L, et al. First-in-human, first-in-child trial of autologous MSCs carrying the oncolytic virus icovir-5 in patients with advanced tumor. Molecular therapy 2020; 28(4): 1033-42.
[114]
El Haddad N, Heathcote D, Moore R, et al. Mesenchymal stem cells express serine protease inhibitor to evade the host immune response. Blood 2011; 117(4): 1176-83.
[http://dx.doi.org/10.1182/blood-2010-06-287979] [PMID: 21076046]
[115]
Schu S, Nosov M, O’Flynn L, et al. Immunogenicity of allogeneic mesenchymal stem cells. J Cell Mol Med 2012; 16(9): 2094-103.
[http://dx.doi.org/10.1111/j.1582-4934.2011.01509.x] [PMID: 22151542]
[116]
Zha S, Tay JCK, Zhu S, Li Z, Du Z, Wang S. Generation of mesenchymal stromal cells with low immunogenicity from Human PBMC-derived β2 microglobulin knockout induced pluripotent stem cells. Cell Transplant 2020; 29: 0963689720965529.
[http://dx.doi.org/10.1177/0963689720965529] [PMID: 33172291]
[117]
Giuliani M, Bennaceur-Griscelli A, Nanbakhsh A, et al. TLR ligands stimulation protects MSC from NK killing. Stem Cells 2014; 32(1): 290-300.
[http://dx.doi.org/10.1002/stem.1563] [PMID: 24123639]
[118]
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.
[http://dx.doi.org/10.1182/blood-2005-07-2775] [PMID: 16239427]
[119]
Lee JM. When CAR meets stem cells. Int J Mol Sci 2019; 20(8): 1825.
[http://dx.doi.org/10.3390/ijms20081825] [PMID: 31013813]
[120]
Yan C, Li S, Li Z, et al. Human umbilical cord mesenchymal stem cells as vehicles of CD20-specific TRAIL fusion protein delivery: A double-target therapy against non-Hodgkin’s lymphoma. Mol Pharm 2013; 10(1): 142-51.
[http://dx.doi.org/10.1021/mp300261e] [PMID: 23121392]
[121]
Balyasnikova IV, Franco-Gou R, Mathis JM, Lesniak MS. Genetic modification of mesenchymal stem cells to express a single-chain antibody against EGFRvIII on the cell surface. J Tissue Eng Regen Med 2010; 4(4): 247-58.
[http://dx.doi.org/10.1002/term.228] [PMID: 19937911]
[122]
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(1): 12.
[http://dx.doi.org/10.1186/1757-2215-3-12] [PMID: 20500878]
[123]
Golinelli G, Grisendi G, Prapa M, et al. Targeting GD2-positive glioblastoma by chimeric antigen receptor empowered mesenchymal progenitors. Cancer Gene Ther 2020; 27(7-8): 558-70.
[http://dx.doi.org/10.1038/s41417-018-0062-x] [PMID: 30464207]

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