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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Paclitaxel Priming of TRAIL Expressing Mesenchymal Stromal Cells (MSCs- TRAIL) Increases Antitumor Efficacy of Their Secretome

Author(s): Valentina Coccè, Arianna Bonomi, Loredana Cavicchini, Francesca Sisto, Aldo Giannì, Giampietro Farronato, Giulio Alessandri, Francesco Petrella, Valeria Sordi, Eugenio Parati, Gianpietro Bondiolotti, Francesca Paino and Augusto Pessina*

Volume 21, Issue 3, 2021

Published on: 16 November, 2020

Page: [213 - 222] Pages: 10

DOI: 10.2174/1568009620666201116112153

Price: $65

Abstract

Background: Adipose tissue-derived MSCs engineered with the tumor necrosis factor- related apoptosis-inducing ligand protein (MSCs-TRAIL) have significant anticancer activity. MSCs, without any genetic modifications, exposed to high doses of chemotherapeutic agents are able to uptake the drug and release it in an amount affecting tumor proliferation. The purpose of this study was to verify the ability of MSCs-TRAIL to uptake and release paclitaxel (PTX) by providing an increased antitumor efficacy.

Methods: MSCs and MSCs-TRAIL were tested for their sensitivity to Paclitaxel (PTX) by MTT assay, and the cells were loaded with PTX according to a standardized procedure. The secretome was analysed by HPLC for the presence of PTX, microarray assay for soluble TRAIL (s-TRAIL) and tested for in vitro anticancer activity.

Results: MSCs-TRAIL were resistant to PTX and able to incorporate and then release the drug. The secretion of s-TRAIL by PTX loaded MSCs-TRAIL was not inhibited, and the PTX delivery together with s-TRAIL secretion resulted in increased antitumor efficacy of cell secretome as tested in vitro on human pancreatic carcinoma (CFPAC-1) and glioblastoma (U87-MG).

Conclusion: Our result is the first demonstration of the possible merging of two new MSCs therapy approaches based on genetic manipulation and drug delivery. If confirmed in vivo, this could potentiate the efficacy of MSCs-TRAIL and strongly contribute to reducing the toxicity due to the systemic treatment of PTX.

Keywords: TRAIL-Mesenchymal stromal cells, drug delivery mechanism, paclitaxel, secretome, U87-MG, CFPac-1.

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[1]
Gnecchi, M.; Zhang, Z.; Ni, A.; Dzau, V.J. Paracrine mechanisms in adult stem cell signaling and therapy. Circ. Res., 2008, 103(11), 1204-1219.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.176826] [PMID: 19028920]
[2]
Biancone, L.; Bruno, S.; Deregibus, M.C.; Tetta, C.; Camussi, G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol. Dial. Transplant., 2012, 27(8), 3037-3042.
[http://dx.doi.org/10.1093/ndt/gfs168] [PMID: 22851627]
[3]
Patel, D.M.; Shah, J.; Srivastava, A.S. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int., 2013, 2013, 496218.
[http://dx.doi.org/10.1155/2013/496218] [PMID: 23577036]
[4]
Aronin, C.E.P.; Tuan, R.S. Therapeutic potential of the immunomodulatory activities of adult mesenchymal stem cells. Birth Defects Res. Part C-Embryo Today-Rev., 2010, 90, 67-74.
[http://dx.doi.org/10.1002/bdrc.20174]
[5]
Zhang, Y.; Yan, W.; Collins, M.A.; Bednar, F.; Rakshit, S.; Zetter, B.R.; Stanger, B.Z.; Chung, I.; Rhim, A.D.; di Magliano, M.P. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res., 2013, 73 (20 ), 6359 -6374 .
[http://dx.doi.org/10.1158/0008-5472.CAN-13-1558-T]
[6]
Li, N.; Hua, J. Interactions between mesenchymal stem cells and the immune system. Cell. Mol. Life Sci., 2017, 74(13), 2345-2360.
[http://dx.doi.org/10.1007/s00018-017-2473-5] [PMID: 28214990]
[7]
Crivelli, B.; Chlapanidas, T.; Perteghella, S.; Lucarelli, E.; Pascucci, L.; Brini, A.T.; Ferrero, I.; Marazzi, M.; Pessina, A.; Torre, M.L. Italian Mesenchymal Stem Cell Group (GISM). Mesenchymal stem/stromal cell extracellular vesicles: From active principle to next generation drug delivery system. J. Control. Release, 2017, 262(262), 104-117.
[http://dx.doi.org/10.1016/j.jconrel.2017.07.023] [PMID: 28736264]
[8]
Lin, W.; Huang, L.; Li, Y.; Fang, B.; Li, G.; Chen, L.; Xu, L. Mesenchymal stem cells and cancer: clinical challenges and opportunities. Biomed Res Int., 2019, 8, 8280853.
[9]
Belmar-Lopez, C.; Mendoza, G.; Oberg, D.; Burnet, J.; Simon, C.; Cervello, I.; Iglesias, M.; Ramirez, J.C.; Lopez-Larrubia, P.; Quintanilla, M.; Martin-Duque, P. Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth. BMC Med., 2013, 28 (11 ), 139 .
[10]
Reagan, M.R.; Kaplan, D.L. Concise review: Mesenchymal stem cell tumor-homing: detection methods in disease model systems. Stem Cells, 2011, 29(6), 920-927.
[http://dx.doi.org/10.1002/stem.645] [PMID: 21557390]
[11]
Park, J.S.; Suryaprakash, S.; Lao, Y.H.; Leong, K.W. Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods, 2015, 84, 3-16.
[http://dx.doi.org/10.1016/j.ymeth.2015.03.002] [PMID: 25770356]
[12]
Sasportas, L.S.; Kasmieh, R.; Wakimoto, H.; Hingtgen, S.; van de Water, J.A.; Mohapatra, G.; Figueiredo, J.L.B.; Martuza, R.L.; Weissleder, R.; Shah, K. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc. Natl. Acad. Sci. USA, 2009, 106(12), 4822-4827.
[http://dx.doi.org/10.1073/pnas.0806647106] [PMID: 19264968]
[13]
Shah, K. Mesenchymal stem cells engineered for cancer therapy. Adv. Drug Deliv. Rev., 2012, 64(8), 739-748.
[http://dx.doi.org/10.1016/j.addr.2011.06.010] [PMID: 21740940]
[14]
Stuckey, D.W.; Shah, K. TRAIL on trial: preclinical advances in cancer therapy. Trends Mol. Med., 2013, 19(11), 685-694.
[http://dx.doi.org/10.1016/j.molmed.2013.08.007] [PMID: 24076237]
[15]
Sage, E.K.; Thakrar, R.M.; Janes, S.M. Genetically modified mesenchymal stromal cells in cancer therapy. Cytotherapy, 2016, 18(11), 1435-1445.
[http://dx.doi.org/10.1016/j.jcyt.2016.09.003] [PMID: 27745603]
[16]
Niess, H.; von Einem, J.C.; Thomas, M.N.; Michl, M.; Angele, M.K.; Huss, R.; Günther, C.; Nelson, P.J.; Bruns, C.J.; Heinemann, V. Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial. BMC Cancer., 2015, 8 (15 ), 237 .
[17]
Schweizer, M.T.; Wang, H.; Bivalacqua, T.J.; Partin, A.W.; Lim, S.J.; Chapman, C.; Abdallah, R.; Levy, O.; Bhowmick, N.A.; Karp, J.M.; De Marzo, A.; Isaacs, J.T.; Brennen, W.N.; Denmeade, S.R. 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), 441-449.
[http://dx.doi.org/10.1002/sctm.18-0230] [PMID: 30735000]
[18]
Nowakowski, A.; Drela, K.; Rozycka, J.; Janowski, M.; Lukomska, B. Engineered mesenchymal stem cells as an anti-cancer trojan horse. Stem Cells Dev., 2016, 25(20), 1513-1531.
[http://dx.doi.org/10.1089/scd.2016.0120] [PMID: 27460260]
[19]
Shi, J.; Zheng, D.; Man, K.; Fan, S.T.; Xu, R. TRAIL: a potential agent for cancer therapy. Curr. Mol. Med., 2003, 3(8), 727-736.
[http://dx.doi.org/10.2174/1566524033479401] [PMID: 14682494]
[20]
Kruyt, F.A. TRAIL and cancer therapy. Cancer Lett., 2008, 263(1), 14-25.
[http://dx.doi.org/10.1016/j.canlet.2008.02.003] [PMID: 18329793]
[21]
Grisendi, G.; Bussolari, R.; Cafarelli, L.; Petak, I.; Rasini, V.; Veronesi, E.; De Santis, G.; Spano, C.; Tagliazzucchi, M.; Barti-Juhasz, H.; Scarabelli, L.; Bambi, F.; Frassoldati, A.; Rossi, G.; Casali, C.; Morandi, U.; Horwitz, E.M.; Paolucci, P.; Conte, P.; Dominici, M. Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res., 2010, 70(9), 3718-3729.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-1865] [PMID: 20388793]
[22]
Moniri, M.R.; Sun, X.Y.; Rayat, J.; Dai, D.; Ao, Z.; He, Z.; Verchere, C.B.; Dai, L.J.; Warnock, G.L. TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells. Cancer Gene Ther., 2012, 19(9), 652-658.
[http://dx.doi.org/10.1038/cgt.2012.46] [PMID: 22767216]
[23]
Spano, C.; Grisendi, G.; Golinelli, G.; Rossignoli, F.; Prapa, M.; Bestagno, M.; Candini, O.; Petrachi, T.; Recchia, A.; Miselli, F.; Rovesti, G.; Orsi, G.; Maiorana, A.; Manni, P.; Veronesi, E; Piccinno, M.S.; Murgia, A.; Pinelli, M.; Horwitz, E.M.; Cascinu, S.; Conte, P.; Dominici, M. Soluble TRAIL Armed Human MSC As Gene Therapy For Pancreatic Cancer. Sci Rep., 2019, 9(1), 1788.
[http://dx.doi.org/10.1038/s41598-018-37433-6]
[24]
Song, K.; Benhaga, N.; Anderson, R.L.; Khosravi-Far, R. Transduction of tumor necrosis factor-related apoptosis-inducing ligand into hematopoietic cells leads to inhibition of syngeneic tumor growth in vivo. Cancer Res., 2006, 66 (12), 6304-6311.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-3501]
[25]
Wang, S.S.; Feng, L.; Hu, B.G.; Lu, Y.F.; Wang, W.M.; Guo, W.; Suen, C.W.; Jiao, B.H.; Pang, J.X.; Fu, W.M.; Zhang, J.F. mir-133a promotes trail resistance in glioblastoma via suppressing death receptor 5 and activating NF-κB signaling. Mol. Ther. Nucleic Acids, 2017, 8(8), 482-492.
[http://dx.doi.org/10.1016/j.omtn.2017.07.015] [PMID: 28918048]
[26]
Pessina, A.; Bonomi, A.; Coccè, V.; Invernici, G.; Navone, S.; Cavicchini, L.; Sisto, F.; Ferrari, M.; Viganò, L.; Locatelli, A; Ciusani, E.; Cappelletti, G.; Cartelli, D.; Arnaldo, C.; Parati, E.; Marfia, G.; Pallini, R.; Falchetti, M.L.; Alessandri, G. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One., 2011, 6 (12 ), 28321 .
[27]
Bonomi, A.; Coccè, V.; Cavicchini, L.; Sisto, F.; Dossena, M.; Balzarini, P.; Portolani, N.; Ciusani, E.; Parati, E.; Alessandri, G.; Pessina, A. Adipose tissue-derived stromal cells primed in vitro with paclitaxel acquire anti-tumor activity. Int. J. Immunopathol. Pharmacol., 2013, 26(1)(Suppl.), 33-41.
[http://dx.doi.org/10.1177/03946320130260S105] [PMID: 24046947]
[28]
Pascucci, L.; Coccè, V.; Bonomi, A.; Ami, D.; Ceccarelli, P.; Ciusani, E.; Viganò, L.; Locatelli, A.; Sisto, F.; Doglia, S.M.; Parati, E.; Bernardo, M.E.; Muraca, M.; Alessandri, G.; Bondiolotti, G.; Pessina, A. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J. Control. Release, 2014, 192(192), 262-270.
[http://dx.doi.org/10.1016/j.jconrel.2014.07.042] [PMID: 25084218]
[29]
Pessina, A.; Leonetti, C.; Artuso, S.; Benetti, A.; Dessy, E.; Pascucci, L.; Passeri, D.; Orlandi, A.; Berenzi, A.; Bonomi, A.; Coccè, V.; Ceserani, V.; Ferri, A.; Dossena, M.; Mazzuca, P.; Ciusani, E.; Ceccarelli, P.; Caruso, A.; Portolani, N.; Sisto, F.; Parati, E.; Alessandri, G. Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model. J Exp Clin Cancer Res. , 2015, 13 , 34 -82 .
[30]
Bonomi, A.; Silini, A.; Vertua, E.; Signoroni, P.B.; Coccè, V.; Cavicchini, L.; Sisto, F.; Alessandri, G.; Pessina, A.; Parolini, O. Human amniotic mesenchymal stromal cells (hAMSCs) as potential vehicles for drug delivery in cancer therapy: an in vitro study. Stem Cell Res Ther., 2015, 28, 6-155.
[31]
Brini, A.T.; Coccè, V.; Ferreira, L.M.; Giannasi, C.; Cossellu, G.; Giannì, A.B.; Angiero, F.; Bonomi, A.; Pascucci, L.; Falchetti, M.L.; Ciusani, E.; Bondiolotti, G.; Sisto, F.; Alessandri, G.; Pessina, A.; Farronato, G. Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel. Expert Opin. Drug Deliv., 2016, 13(6), 789-798.
[http://dx.doi.org/10.1517/17425247.2016.1167037] [PMID: 26986001]
[32]
Nolta, J.A. “Next-generation” mesenchymal stem or stromal cells for the in vivo delivery of bioactive factors: progressing toward the clinic. Transfusion, 2016, 56(4), 15S-17S.
[http://dx.doi.org/10.1111/trf.13564] [PMID: 27079315]
[33]
Rimoldi, I.; Coccè, V.; Facchetti, G.; Alessandri, G.; Brini, A.T.; Sisto, F.; Parati, E.; Cavicchini, L.; Lucchini, G.; Petrella, F.; Ciusani, E.; Pessina, A. Uptake-release by MSCs of a cationic platinum(II) complex active in vitro on human malignant cancer cell lines. Biomed. Pharmacother., 2018, 108, 111-118.
[http://dx.doi.org/10.1016/j.biopha.2018.09.040] [PMID: 30218855]
[34]
Scioli, M.G.; Artuso, S.; D'Angelo, C.; Porru, M.; D'Amico, F.; Bielli, A.; Gentile, P.; Cervelli, V.; Leonetti, C.; Orlandi, A. Adipose-derived stem cell-mediated paclitaxel delivery inhibits breast cancer growth. PLoS One., 2018, 13(9), 0203426.
[35]
Rossignoli, F.; Spano, C.; Grisendi, G.; Foppiani, E.M.; Golinelli, G.; Mastrolia, I.; Bestagno, M.; Candini, O.; Petrachi, T.; Recchia, A.; Miselli, F.; Rovesti, G.; Orsi, G.; Veronesi, E; Medici, G.; Petocchi, B.; Pinelli, M.; Horwitz, E.M.; Conte, P.; Dominici, M. MSC-Delivered Soluble TRAIL and Paclitaxel as Novel Combinatory Treatment for Pancreatic Adenocarcinoma. Theranostics., 2019, 9(2), 436-448.
[36]
Ferlay, J.; Steliarova-Foucher, E.; Lortet-Tieulent, J.; Rosso, S.; Coebergh, J.W.; Comber, H.; Forman, D.; Bray, F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur. J. Cancer, 2013, 49(6), 1374-1403.
[http://dx.doi.org/10.1016/j.ejca.2012.12.027] [PMID: 23485231]
[37]
Di Carlo, D.T.; Cagnazzo, F.; Benedetto, N.; Morganti, R.; Perrini, P. Multiple high-grade gliomas: Epidemiology, management, and outcome. A systematic review and meta-analysis. Neurosurg. Rev., 2017, 1-13.
[PMID: 29138949]
[38]
McIntosh, J.C.; Schoumacher, R.A.; Tiller, R.E. Pancreatic adenocarcinoma in a patient with cystic fibrosis. Am. J. Med., 1988, 85(4), 592.
[http://dx.doi.org/10.1016/S0002-9343(88)80116-5] [PMID: 3177424]
[39]
Schoumacher, R.A.; Ram, J.; Iannuzzi, M.C.; Bradbury, N.A.; Wallace, R.W.; Hon, C.T.; Kelly, D.R.; Schmid, S.M.; Gelder, F.B.; Rado, T.A. A cystic fibrosis pancreatic adenocarcinoma cell line. Proc. Natl. Acad. Sci. USA, 1990, 87(10), 4012-4016.
[http://dx.doi.org/10.1073/pnas.87.10.4012] [PMID: 1692630]
[40]
Fogh, J.; Fogh, J.M.; Orfeo, T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J. Natl. Cancer Inst., 1977, 59(1), 221-226.
[http://dx.doi.org/10.1093/jnci/59.1.221] [PMID: 327080]
[41]
Olopade, O.I.; Jenkins, R.B.; Ransom, D.T.; Malik, K.; Pomykala, H.; Nobori, T.; Cowan, J.M.; Rowley, J.D.; Diaz, M.O. Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas. Cancer Res., 1992, 52(9), 2523-2529.
[PMID: 1568221]
[42]
Ceserani, V.; Ferri, A.; Berenzi, A.; Benetti, A.; Ciusani, E.; Pascucci, L.; Bazzucchi, C.; Coccè, V.; Bonomi, A.; Pessina, A.; Ghezzi, E.; Zeira, O.; Ceccarelli, P.; Versari, S.; Tremolada, C.; Alessandri, G. Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vasc. Cell, 2016, 8, 3.
[http://dx.doi.org/10.1186/s13221-016-0037-3] [PMID: 27547374]
[43]
Coccè, V.; Brini, A.; Giannì, A.B.; Sordi, V.; Berenzi, A.; Alessandri, G.; Tremolada, C.; Versari, S.; Bosetto, A.; Pessina, A. A nonenzymatic and automated closed-cycle process for the isolation of mesenchymal stromal cells in drug delivery applications. Stem Cells Int., 2018, 2018(20), 4098140.
[http://dx.doi.org/10.1155/2018/4098140] [PMID: 29531535]
[44]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]
[45]
Pessina, A.; Gribaldo, L.; Mineo, E.; Neri, M.G. In vitro short-term and long-term cytotoxicity of fluoroquinolones on murine cell lines. Indian J. Exp. Biol., 1994, 32(2), 113-118.
[PMID: 8045610]
[46]
Reed, L.J.; Muench, H. A simple method of estimating fifty percent endpoints. Am. J. Hyg., 1938, 27, 493-497.
[47]
Mariotti, M.; Colognato, R.; Rimoldi, M.; Rizzetto, M.; Sisto, F.; Coccè, V.; Bonomi, A.; Parati, E.; Alessandri, G.; Bagnati, R.; Pessina, A. Mesenchymal stromal cells uptake and release paclitaxel without reducing its anticancer activity. Anticancer. Agents Med. Chem., 2015, 15(3), 400-405.
[http://dx.doi.org/10.2174/1871520614666140618113441] [PMID: 24942547]
[48]
Bosco, D.B.; Kenworthy, R.; Zorio, D.A.; Sang, Q.X. Human mesenchymal stem cells are resistant to Paclitaxel by adopting a non-proliferative fibroblastic state. PLoS One, 2015, 10(6), e0128511.
[http://dx.doi.org/10.1371/journal.pone.0128511] [PMID: 26029917]
[49]
Gyamfi, J.; Eom, M.; Koo, J.S.; Choi, J. Multifaceted Roles of Interleukin-6 in Adipocyte-Breast Cancer Cell Interaction. Transl. Oncol., 2018, 11(2), 275-285.
[http://dx.doi.org/10.1016/j.tranon.2017.12.009] [PMID: 29413760]
[50]
Zhang, B.; Yin, Y.; Lai, R.C.; Tan, S.S.; Choo, A.B.; Lim, S.K. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. , 2014, 23 (11 ), 1233 -44 .
[http://dx.doi.org/10.1089/scd.2013.0479]
[51]
Shan, Y.; He, X.; Song, W.; Han, D.; Niu, J.; Wang, J. Role of IL-6 in the invasiveness and prognosis of glioma. Int J Clin Exp Med. , 2015, 8(6), 9114-9120.
[52]
Pascucci, L.; Coccè, V.; Bonomi, A.; Ami, D.; Ceccarelli, P.; Ciusani, E.; Viganò, L.; Locatelli, A.; Sisto, F.; Doglia, S. M.; Parati, E.; Bernardo, M. E.; Muraca, M.; Alessandri, G.; Bondiolotti, G.; Pessina, A. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J. Control. Release, 2014, 192, 262-270.
[http://dx.doi.org/10.1016/j.jconrel.2014.07.042]
[53]
Coccè, V.; Franzè, S.; Brini, A.T.; Giannì, A.B.; Pascucci, L.; Ciusani, E.; Alessandri, G.; Farronato, G.; Cavicchini, L.; Sordi, V.; Paroni, R.; Dei Cas, M.; Cilurzo, F.; Pessina, A. In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel. Pharmaceutics, 2019, 11(2), 61.
[http://dx.doi.org/10.3390/pharmaceutics11020061] [PMID: 30717104]
[54]
Sage, E.K.; Kolluri, K.K.; McNulty, K.; Lourenco, Sda.S.; Kalber, T.L.; Ordidge, K.L.; Davies, D.; Gary Lee, Y.C.; Giangreco, A.; Janes, S.M. Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma. Thorax, 2014, 69(7), 638-647.
[http://dx.doi.org/10.1136/thoraxjnl-2013-204110] [PMID: 24567297]

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