Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249.
   PubMed Web of Science ®Google Scholar
• Sun J, Wei Q, Zhou Y, et al. A systematic analysis of FDA-approved anticancer drugs. BMC Syst Biol. 2017;11(S5):87.
   PubMed Web of Science ®Google Scholar
• Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6(8):583–592.
   PubMed Web of Science ®Google Scholar
• Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135–146.
   PubMed Web of Science ®Google Scholar
• Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 1986;46:6387–6392.
   PubMed Web of Science ®Google Scholar
• Matsumura Y. Cancer stromal targeting (CAST) therapy. Adv Drug Deliv Rev. 2012;64(8):710–719.
   PubMed Web of Science ®Google Scholar
• Dong H, Xu X, Wang L, et al. Advances in living cell-based anticancer therapeutics. Biomater Sci. 2020;8(9):2344–2365.
   PubMed Web of Science ®Google Scholar
• Kimbrel EA, Lanza R. Next-generation stem cells - ushering in a new era of cell-based therapies. Nat Rev Drug Discov. 2020;19(7):463–479.
   PubMed Web of Science ®Google Scholar
• Guo L, Zhang Y, Yang Z, et al. Tunneling nanotubular expressways for ultrafast and accurate M1 macrophage delivery of anticancer drugs to metastatic ovarian carcinoma. ACS Nano. 2019;13:1078–1096.
   PubMed Web of Science ®Google Scholar
• Aboody KS, Brown A, Rainov NG, et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci U S A. 2000;97(23):12846–12851.
   PubMed Web of Science ®Google Scholar
• Tabatabai G, Bähr O, Möhle R, et al. Lessons from the bone marrow: how malignant glioma cells attract adult haematopoietic progenitor cells. Brain. 2005;28(9):2200–2211.
   Web of Science ®Google Scholar
• Bagó JR, Okolie O, Dumitru R, et al. Tumor-homing cytotoxic human induced neural stem cells for cancer therapy. Sci Transl Med. 2017;9(375):eaah6510.
   PubMed Web of Science ®Google Scholar
• 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):315–317.
   PubMed Web of Science ®Google Scholar
• Cheng S, Nethi SK, Rathi S, et al. Engineered mesenchymal stem cells for targeting solid tumors: therapeutic potential beyond regenerative therapy. J Pharmacol Exp Ther. 2019;370(2):231–241.
   PubMed Web of Science ®Google Scholar
• Wu HH, Zhou Y, Tabata Y, et al. Mesenchymal stem cell-based drug delivery strategy: from cells to biomimetic. J Control Release. 2019;294:102–113.
   PubMed Web of Science ®Google Scholar
• Vodyanik MA, Yu J, Zhang X, et al. A mesoderm-derived precursor for mesenchymal stem and endothelial cells. Cell Stem Cell. 2010;7(6):718–729.
   PubMed Web of Science ®Google Scholar
• Neri S. Genetic stability of mesenchymal stromal cells for regenerative medicine applications: a fundamental biosafety aspect. Int J Mol Sci. 2019;20(10):2406.
   PubMed Web of Science ®Google Scholar
• Barkholt L, Flory E, Jekerle V, et al. Risk of tumorigenicity in mesenchymal stromal cell-based therapies‒bridging scientific observations and regulatory viewpoints. Cytotherapy. 2013;15(7):753–759.
   PubMed Web of Science ®Google Scholar
• Döring M, Cabanillas Stanchi KM, Lenglinger K, et al. Long-term follow-up after the application of mesenchymal stromal cells in children and adolescents with steroid-refractory graft-versus-host disease. Stem Cells Dev. 2021;30(5):234–246.
   PubMed Web of Science ®Google Scholar
• Christodoulou I, Goulielmaki M, Devetzi M, et al. Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review. Stem Cell Res Ther. 2018;9:336.
   PubMed Web of Science ®Google Scholar
• Zhang J, Huang X, Wang H, et al. The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy. Stem Cell Res Ther. 2015;6(1):234.
   PubMed Web of Science ®Google Scholar
• Bexell D, Scheding S, Bengzon J, et al. Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors. Mol Ther. 2010;18(6):1067–1075.
   PubMed Web of Science ®Google Scholar
• Quante M, Tu SP, Tomita H, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 2011;19(2):257–272.
   PubMed Web of Science ®Google Scholar
• Kidd S, Spaeth E, Dembinski JL, et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells. 2009;27(10):2614–2623.
   PubMed Web of Science ®Google Scholar
• Kabat M, Bobkov I, Kumar S, et al. Trends in mesenchymal stem cell clinical trials 2004–2018: Is efficacy optimal in a narrow dose range? Stem Cells Transl Med. 2020;9(1):17–27.
   PubMed Web of Science ®Google Scholar
• Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147.
   PubMed Web of Science ®Google Scholar
• Vangsness CT Jr, Sternberg H, Harris L. Umbilical cord tissue offers the greatest number of harvestable mesenchymal stem cells for research and clinical application: a literature review of different harvest sites. Arthroscopy. 2015;31(9):1836–1843.
   PubMed Web of Science ®Google Scholar
• Fraser JK, Wulur I, Alfonso Z, et al. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 2006;24(4):150–154.
   PubMed Web of Science ®Google Scholar
• Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol. 2006;208(1):64–76.
   PubMed Web of Science ®Google Scholar
• Chatzistamatiou TK, Papassavas AC, Michalopoulos E, et al. Optimizing isolation culture and freezing methods to preserve Wharton’s jelly’s mesenchymal stem cell (MSC) properties: an MSC banking protocol validation for the Hellenic Cord Blood Bank. Transfusion. 2014;54(12):3108–3120.
   PubMed Web of Science ®Google Scholar
• Mohamed-Ahmed S, Fristad I, Lie SA, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison. Stem Cell Res Ther. 2018;9(1):168.
   PubMed Web of Science ®Google Scholar
• Hua J, Gong J, Meng H, et al. Comparison of different methods for the isolation of mesenchymal stem cells from umbilical cord matrix: proliferation and multilineage differentiation as compared to mesenchymal stem cells from umbilical cord blood and bone marrow. Cell Biol Int. 2013;38(2):198–210.
   Web of Science ®Google Scholar
• Neuhuber B, Swanger SA, Howard L, et al. Effects of plating density and culture time on bone marrow stromal cell characteristics. Exp Hematol. 2008;36(9):1176–1185.
   PubMed Web of Science ®Google Scholar
• Kuçi Z, Bönig H, Kreyenberg H, et al. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey. Haematologica. 2016;101(8):985–994.
   PubMed Web of Science ®Google Scholar
• Bloor AJC, Patel A, Griffin JE, et al. Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study. Nat Med. 2020;26(11):1720–1725.
   PubMed Web of Science ®Google Scholar
• Zangi L, Margalit R, Reich-Zeliger S, et al. Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells. Stem Cells. 2009;27(11):2865–2874.
   PubMed Web of Science ®Google Scholar
• Ruano D, López-Martín JA, Moreno L, et al. First-in-human, first-in-child trial of autologous MSCs carrying the oncolytic virus Icovir-5 in patients with advanced tumors. Mol Ther. 2020;28(4):1033–1042.
   PubMed Web of Science ®Google Scholar
• Krueger TEG, Thorek DLJ, Denmeade SR, et al. Concise review: mesenchymal stem cell-based drug delivery: the good, the bad, the ugly, and the promise. Stem Cells Transl Med. 2018;7(9):651–663.
   PubMed Web of Science ®Google Scholar
• Nitzsche F, Müller C, Lukomska B, et al. Concise review: MSC adhesion cascade-insights into homing and transendothelial migration. Stem Cells. 2017;35(6):1446–1460.
   PubMed Web of Science ®Google Scholar
• Ullah M, Liu DD, Thakor AS. Mesenchymal stromal cell homing: mechanisms and strategies for improvement. iScience. 2019;15:421–438.
   PubMed Web of Science ®Google Scholar
• Lourenco S, Teixeira VH, Kalber T, et al. Macrophage migration inhibitory factor-CXCR4 is the dominant chemotactic axis in human mesenchymal stem cell recruitment to tumors. J Immunol. 2015;194(7):3463–3474.
   PubMed Web of Science ®Google Scholar
• Feng Y, Zhu M, Dangelmajer S, et al. Hypoxia-cultured human adipose-derived mesenchymal stem cells are non-oncogenic and have enhanced viability, motility, and tropism to brain cancer. Cell Death Dis. 2014;5(12):e1567.
   PubMed Web of Science ®Google Scholar
• Smith CL, Chaichana KL, Lee YM, et al. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer. Stem Cells Transl Med. 2015;4(3):239–251.
   PubMed Web of Science ®Google Scholar
• Zhang T, Xu Q, Huang T, et al. New insights into biocompatible iron oxide nanoparticles: a potential booster of gene delivery to stem cells. Small. 2020;16(37):e2001588.
   PubMed Web of Science ®Google Scholar
• Arbab AS, Jordan EK, Wilson LB, et al. In Vivo Trafficking and Targeted Delivery of Magnetically Labeled Stem Cells. Hum Gene Ther. 2004;15(4):351–360.
   PubMed Web of Science ®Google Scholar
• Kono Y, Takegaki J, Ohba T, et al. Magnetization of mesenchymal stem cells using magnetic liposomes enhances their retention and immunomodulatory efficacy in mouse inflamed skeletal muscle. Int J Pharm. 2021;596:120298.
   PubMed Web of Science ®Google Scholar
• Ahn YJ, Kong TH, Choi JS, et al. Strategies to enhance efficacy of SPION-labeled stem cell homing by magnetic attraction: a systemic review with meta-analysis. Int J Nanomedicine. 2019;14:4849–4866.
   PubMed Web of Science ®Google Scholar
• Xu C, Feng Q, Yang H, et al. A light-triggered mesenchymal stem cell delivery system for photoacoustic imaging and chemo-photothermal therapy of triple negative breast cancer. Adv Sci (Weinh). 2018;5(10):1800382.
   PubMedGoogle Scholar
• Silva LHA, Silva MC, Vieira JB, et al. Magnetic targeting increases mesenchymal stromal cell retention in lungs and enhances beneficial effects on pulmonary damage in experimental silicosis. Stem Cells Transl Med. 2020;9(10):1244–1256.
   PubMed Web of Science ®Google Scholar
• Mader EK, Butler G, Dowdy SC, et al. Optimizing patient derived mesenchymal stem cells as virus carriers for a phase I clinical trial in ovarian cancer. J Transl Med. 2013;11(1):20.
   PubMed Web of Science ®Google Scholar
• Malekshah OM, Sarkar S, Nomani A, et al. Bioengineered adipose-derived stem cells for targeted enzyme-prodrug therapy of ovarian cancer intraperitoneal metastasis. J Control Release. 2019;311–312:273–287.
   PubMed Web of Science ®Google Scholar
• 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):2068–2073.
   PubMed Web of Science ®Google Scholar
• Rincón E, Cejalvo T, Kanojia D, et al. Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model. Oncotarget. 2017;8(28):45415–45431.
   PubMedGoogle Scholar
• Kusamori K, Nishikawa M, Mizuno N, et al. Transplantation of insulin-secreting multicellular spheroids for the treatment of type 1 diabetes in mice. J Control Release. 2014;173:119–124.
   PubMed Web of Science ®Google Scholar
• Suryaprakash S, Lao YH, Cho HY, et al. Engineered mesenchymal stem cell/nanomedicine spheroid as an active drug delivery platform for combinational glioblastoma therapy. Nano Lett. 2019;19(3):1701–1705.
   PubMed Web of Science ®Google Scholar
• Wang S, Guo L, Ge J, et al. Excess integrins cause lung entrapment of mesenchymal stem cells. Stem Cells. 2015;33(11):3315–3326.
   PubMed Web of Science ®Google Scholar
• Kim JC, Tae G. The modulation of biodistribution of stem cells by anchoring lipid-conjugated heparin on the cell surface. J Control Release. 2015;217:128–137.
   PubMed Web of Science ®Google Scholar
• Moll G, Ankrum JA, Kamhieh-Milz J, et al. Intravascular mesenchymal stromal/stem cell therapy product diversification: time for new clinical guidelines. Trends Mol Med. 2019;25(2):149–163.
   PubMed Web of Science ®Google Scholar
• Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459–466.
   PubMed Web of Science ®Google Scholar
• Huang WC, Lu IL, Chiang WH, et al. Tumortropic adipose-derived stem cells carrying smart nanotherapeutics for targeted delivery and dual-modality therapy of orthotopic glioblastoma. J Control Release. 2017;254:119–130.
   PubMed Web of Science ®Google Scholar
• Nakamizo A, Marini F, Amano T, et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res. 2005;65(8):3307–3318.
   PubMed Web of Science ®Google Scholar
• Li G, Bonamici N, Dey M, et al. Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies. Expert Opin Drug Deliv. 2018;15(2):163–172.
   PubMed Web of Science ®Google Scholar
• Takayama Y, Kusamori K, Hayashi M, et al. Long-term drug modification to the surface of mesenchymal stem cells by the avidin-biotin complex method. Sci Rep. 2017;7(1):16953.
   PubMed Web of Science ®Google Scholar
• Dhada KS, Hernandez DS, Suggs LJ. In Vivo photoacoustic tracking of mesenchymal stem cell viability. ACS Nano. 2019;13(7):7791–7799.
   PubMed Web of Science ®Google Scholar
• Leibacher J, Henschler R. Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells. Stem Cell Res Ther. 2016;7(1):7.
   PubMed Web of Science ®Google Scholar
• de Witte SFH, Luk F, Sierra Parraga JM, et al. Immunomodulation by therapeutic mesenchymal stromal cells (MSC) is triggered through phagocytosis of MSC by monocytic cells. Stem Cells. 2018;36(4):602–615.
   PubMed Web of Science ®Google Scholar
• Preda MB, Neculachi CA, Fenyo IM, et al. Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice. Cell Death Dis. 2021;12:566.
   PubMed Web of Science ®Google Scholar
• Raz Y, Cohen N, Shani O, et al. Bone marrow-derived fibroblasts are a functionally distinct stromal cell population in breast cancer. J Exp Med. 2018;215(12):3075–3093.
   PubMed Web of Science ®Google Scholar
• Zhao R, Chen X, Song H, et al. Dual role of MSC-derived exosomes in tumor development. Stem Cells Int. 2020;2020:8844730.
   PubMed Web of Science ®Google Scholar
• Roccaro AM, Sacco A, Maiso P, et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest. 2013;123(4):1542–1555.
   PubMed Web of Science ®Google Scholar
• Biswas S, Mandal G, Roy Chowdhury S, et al. Exosomes produced by mesenchymal stem cells drive differentiation of myeloid cells into immunosuppressive M2-polarized macrophages in breast bancer. J Immunol. 2019;203(12):3447–3460.
   PubMed Web of Science ®Google Scholar
• Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174–186.
   PubMed Web of Science ®Google Scholar
• Jotzu C, Alt E, Welte G, et al. Adipose tissue-derived stem cells differentiate into carcinoma-associated fibroblast-like cells under the influence of tumor-derived factors. Anal Cell Pathol (Amst). 2010;33(2):61–79.
   PubMedGoogle Scholar
• Strong AL, Pei DT, Hurst CG, et al. Obesity enhances the conversion of adipose-derived stromal/stem cells into carcinoma-associated fibroblast leading to cancer cell proliferation and progression to an invasive phenotype. Stem Cells Int. 2017;2017:9216502.
   PubMed Web of Science ®Google Scholar
• Ridge SM, Sullivan FJ, Glynn SA. Mesenchymal stem cells: key players in cancer progression. Mol Cancer. 2017;16(1):31.
   PubMed Web of Science ®Google Scholar
• Théry C, Witwer KW, Aikawa E. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guideline. J Extracell Vesicles. 2018;7:1535750.
   PubMed Web of Science ®Google Scholar
• Chen D, Tang P, Liu L, et al. Bone marrow-derived mesenchymal stem cells promote cell proliferation of multiple myeloma through inhibiting T cell immune responses via PD-1/PD-L1 pathway. Cell Cycle. 2018;17(7):858–867.
   PubMed Web of Science ®Google Scholar
• Chen J, Ji T, Wu D, et al. Author correction: 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(7):488.
   PubMed Web of Science ®Google Scholar
• Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
   PubMed Web of Science ®Google Scholar
• Huntington ND, Cursons J, Rautela J. The cancer-natural killer cell immunity cycle. Nat Rev Cancer. 2020;20(8):437–454.
   PubMed Web of Science ®Google Scholar
• Yu Y, Liu Y, Zong C, et al. Mesenchymal stem cells with Sirt1 overexpression suppress breast tumor growth via chemokine-dependent natural killer cells recruitment. Sci Rep. 2016;6(1):35998.
   PubMed Web of Science ®Google Scholar
• Li X, Chen M, Lu W, et al. Targeting FAPα-expressing tumor-associated mesenchymal stromal cells inhibits triple-negative breast cancer pulmonary metastasis. Cancer Lett. 2021;503:32–42.
   PubMed Web of Science ®Google Scholar
• Studeny M, Marini FC, Champlin RE, et al. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res. 2002;62:3603–3608.
   PubMed Web of Science ®Google Scholar
• Tsujimura M, Kusamori K, Oda C, et al. Regulation of proliferation and functioning of transplanted cells by using herpes simplex virus thymidine kinase gene in mice. J Control Release. 2018;275:78–84.
   PubMed Web of Science ®Google Scholar
• Niess H, Bao Q, Conrad C, et al. Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma. Ann Surg. 2011;254(5):767–774.
   PubMed Web of Science ®Google Scholar
• Yan C, Yang M, Li Z, et al. Suppression of orthotopically implanted hepatocarcinoma in mice by umbilical cord-derived mesenchymal stem cells with sTRAIL gene expression driven by AFP promoter. Biomaterials. 2014;35:3035–3043.
   PubMed Web of Science ®Google Scholar
• von 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):1538–1546.
   PubMed Web of Science ®Google Scholar
• Moreno R. Mesenchymal stem cells and oncolytic viruses: joining forces against cancer. J Immunother Cancer. 2021;9(2):e001684.
   PubMed Web of Science ®Google Scholar
• Hammer K, Kazcorowski A, Liu L, et al. Engineered adenoviruses combine enhanced oncolysis with improved virus production by mesenchymal stromal carrier cells. Int J Cancer. 2015;137(4):978–990.
   PubMed Web of Science ®Google Scholar
• Tsujimura M, Kusamori K, Katsumi H, et al. Cell-based interferon gene therapy using proliferation-controllable, interferon-releasing mesenchymal stem cells. Sci Rep. 2019;9(1):18869.
   PubMed Web of Science ®Google Scholar
• Mohme M, Maire CL, Geumann U, et al. Local intracerebral immunomodulation using interleukin-expressing mesenchymal stem cells in glioblastoma. Clin Cancer Res. 2020;26(11):2626–2639.
   PubMed Web of Science ®Google Scholar
• Xu G, Guo Y, Seng Z, et al. Bone marrow-derived mesenchymal stem cells co-expressing interleukin-18 and interferon-β exhibit potent antitumor effect against intracranial glioma in rats. Oncol Rep. 2015;34(4):1915–1922.
   PubMed Web of Science ®Google Scholar
• Wu Z, Liu W, Wang Z, et al. Mesenchymal stem cells derived from iPSCs expressing interleukin-24 inhibit the growth of melanoma in the tumor-bearing mouse model. Cancer Cell Int. 2020;20(1):33.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Zhang J, Hou L, Wu X, et al. Inhibitory effect of genetically engineered mesenchymal stem cells with apoptin on hepatoma cells in vitro and in vivo. Mol Cell Biochem. 2016;416(1–2):193–203.
   PubMed Web of Science ®Google Scholar
• Mangraviti A, Tzeng SY, Gullotti D, et al. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival. Biomaterials. 2016;100:53–66.
   PubMed Web of Science ®Google Scholar
• Lee HK, Finniss S, Cazacu S, et al. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget. 2013;4(2):346–361.
   PubMedGoogle Scholar
• Hanatani T, Takasu N. CiRA iPSC seed stocks (CiRA’s iPSC Stock Project). Stem Cell Res. 2020;50:102033.
   PubMed Web of Science ®Google Scholar
• 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 bells in men with localized prostate cancer. Stem Cells Transl Med. 2019;8(5):441–449.
   PubMed Web of Science ®Google Scholar
• Melen GJ, Franco-Luzón L, Ruano D, et al. Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells. Cancer Lett. 2016;371:161–170.
   PubMed Web of Science ®Google Scholar
• Pascucci L, Coccè V, Bonomi A, et al. 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.
   PubMed Web of Science ®Google Scholar
• Pessina A, Bonomi A, Coccè V, et al. Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy. PLoS One. 2011;6(12):e28321.
   PubMed Web of Science ®Google Scholar
• Kolba MD, Dudka W, Zaręba-Kozioł M, et al. Tunneling nanotube-mediated intercellular vesicle and protein transfer in the stroma-provided imatinib resistance in chronic myeloid leukemia cells. Cell Death Dis. 2019;10(11):817.
   PubMed Web of Science ®Google Scholar
• Bonomi A, Sordi V, Dugnani E, et al. Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells. Cytotherapy. 2015;17(12):1687–1695.
   PubMed Web of Science ®Google Scholar
• Bonomi A, Silini A, Vertua E, et al. Human amniotic mesenchymal stromal cells (hAMSCs) as potential vehicles for drug delivery in cancer therapy: an in vitro study. Stem Cell Res Ther. 2015;6(1):155.
   PubMed Web of Science ®Google Scholar
• Coccè V, Farronato D, Brini AT, et al. Drug loaded gingival mesenchymal stromal cells (GinPa-MSCs) inhibit in vitro proliferation of oral squamous cell carcinoma. Sci Rep. 2017;7(1):9376.
   PubMed Web of Science ®Google Scholar
• Clavreul A, Pourbaghi-Masouleh M, Roger E, et al. Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal? J Exp Clin Cancer Res. 2017;36(1):135.
   PubMed Web of Science ®Google Scholar
• Komarova S, Roth J, Alvarez R, et al. Targeting of mesenchymal stem cells to ovarian tumors via an artificial receptor. J Ovarian Res. 2010;3(1):12.
   PubMed Web of Science ®Google Scholar
• Zhang X, Yao S, Liu C, et al. Tumor tropic delivery of doxorubicin-polymer conjugates using mesenchymal stem cells for glioma therapy. Biomaterials. 2015;39:269–281.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Tang S, Guo J, et al. Targeted delivery of doxorubicin by nano-loaded mesenchymal stem cells for lung melanoma metastases therapy. Sci Rep. 2017;7(1):44758.
   PubMed Web of Science ®Google Scholar
• Wang X, Chen H, Zeng X, et al. Efficient lung cancer-targeted drug delivery via a nanoparticle/MSC system. Acta Pharm Sin B. 2019;9(1):167–176.
   PubMed Web of Science ®Google Scholar
• Cao S, Guo J, He Y, et al. Nano-loaded human umbilical cord mesenchymal stem cells as targeted carriers of doxorubicin for breast cancer therapy. Artif Cells Nanomed Biotechnol. 2018;46(sup1):642–652.
   PubMed Web of Science ®Google Scholar
• Sadhukha T, O’Brien TD, Prabha S. Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. J Control Release. 2014;196:243–251.
   PubMed Web of Science ®Google Scholar
• Moku G, Layek B, Trautman L, et al. Improving payload capacity and anti-tumor efficacy of mesenchymal stem cells using TAT peptide functionalized polymeric nanoparticles. Cancers (Basel). 2019;11(4):491.
   Web of Science ®Google Scholar
• Roger M, Clavreul A, Venier-Julienne MC, et al. Mesenchymal stem cells as cellular vehicles for delivery of nanoparticles to brain tumors. Biomaterials. 2010;31(32):8393–8401.
   PubMed Web of Science ®Google Scholar
• Dai T, Yang E, Sun Y, et al. Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system. Int J Pharm. 2013;456(1):186–194.
   PubMed Web of Science ®Google Scholar
• Cao B, Yang M, Zhu Y, et al. Stem cells loaded with nanoparticles as a drug carrier for in vivo breast cancer therapy. Adv Mater. 2014;26(27):4627–4631.
   PubMed Web of Science ®Google Scholar
• Kang S, Bhang SH, Hwang S, et al. Mesenchymal stem cells aggregate and deliver gold nanoparticles to tumors for photothermal therapy. ACS Nano. 2015;9(10):9678–9690.
   PubMed Web of Science ®Google Scholar
• Levy O, Brennen WN, Han E, et al. A prodrug-doped cellular trojan horse for the potential treatment of prostate cancer. Biomaterials. 2016;91:140–150.
   PubMed Web of Science ®Google Scholar
• Wu J, Liu Y, Tang Y, et al. Synergistic chemo-photothermal therapy of breast cancer by mesenchymal stem cell-encapsulated Yolk-Shell GNR@HPMO-PTX nanospheres. ACS Appl Mater Interfaces. 2016;8(28):17927–17935.
   PubMed Web of Science ®Google Scholar
• Layek B, Sadhukha T, Panyam J, et al. Nano-engineered mesenchymal stem cells Increase therapeutic efficacy of anticancer drug through true active tumor targeting. Mol Cancer Ther. 2018;17(6):1196–1206.
   PubMed Web of Science ®Google Scholar
• Timin AS, Peltek OO, Zyuzin MV, et al. Safe and effective delivery of antitumor drug using mesenchymal stem cells impregnated with submicron carriers. ACS Appl Mater Interfaces. 2019;11(14):13091–13104.
   PubMed Web of Science ®Google Scholar
• Aoki M, Kakimoto K, Goto M, et al. Novel therapeutic approach using drug-loaded adipose-derived stem cells for pancreatic cancer. Sci Rep. 2019;9(1):17971.
   PubMed Web of Science ®Google Scholar
• Huang L, Xu C, Xu P, et al. Intelligent photosensitive mesenchymal stem cells and cell-derived microvesicles for photothermal therapy of prostate cancer. Nanotheranostics. 2018;3(1):41–53.
   PubMedGoogle Scholar
• Lenna S, Bellotti C, Duchi S, et al. Mesenchymal stromal cells mediated delivery of photoactive nanoparticles inhibits osteosarcoma growth in vitro and in a murine in vivo ectopic model. J Exp Clin Cancer Res. 2020;39(1):40.
   PubMed Web of Science ®Google Scholar
• Li L, Guan Y, Liu H, et al. Silica nanorattle-doxorubicin-anchored mesenchymal stem cells for tumor-tropic therapy. ACS Nano. 2011;5(9):7462–7470.
   PubMed Web of Science ®Google Scholar
• Xu M, Asghar S, Dai S, et al. Mesenchymal stem cells-curcumin loaded chitosan nanoparticles hybrid vectors for tumor-tropic therapy. Int J Biol Macromol. 2019;134:1002–1012.
   PubMed Web of Science ®Google Scholar
• Yao S, Li X, Liu J, et al. Maximized nanodrug-loaded mesenchymal stem cells by a dual drug-loaded mode for the systemic treatment of metastatic lung cancer. Drug Deliv. 2017;24(1):1372–1383.
   PubMed Web of Science ®Google Scholar
• Pessina A, Sisto F, Coccè V, et al. A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells. Cell Biol Toxicol. 2011;27(3):169–180.
   PubMed Web of Science ®Google Scholar
• Han N, Li Z, Cai Z, et al. P-glycoprotein overexpression in bone marrow-derived multipotent stromal cells decreases the risk of steroid-induced osteonecrosis in the femoral head. J Cell Mol Med. 2016;20(11):2173–2182.
   PubMed Web of Science ®Google Scholar
• Kim SG, Jeon CH, Suh HS, et al. P-glycoprotein expression in extracellular matrix formation of chondrogenic differentiation of human adult stem cells. Cell Biol Int. 2007;31(9):1042–1048.
   PubMed Web of Science ®Google Scholar
• Bosco DB, Kenworthy R, Zorio DA, et al. Human mesenchymal stem cells are resistant to Paclitaxel by adopting a non-proliferative fibroblastic state. PLoS One. 2015;10(6):e0128511.
   PubMed Web of Science ®Google Scholar
• Layek B, Sehgal D, Argenta PA, et al. Nanoengineering of mesenchymal stem cells via surface modification for efficient cancer therapy. Adv Ther. 2019;2(9):1900043.
   Web of Science ®Google Scholar
• Takayama Y, Kusamori K, Nishikawa M. Click chemistry as a tool for cell engineering and drug delivery. Molecules. 2019;24(1):172.
   Web of Science ®Google Scholar
• Takayama Y, Kusamori K, Tsukimori C, et al. Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy. J Control Release. 2021;329:1090–1101.
   PubMed Web of Science ®Google Scholar
• Robb KP, Fitzgerald JC, Barry F, et al. Mesenchymal stromal cell therapy: progress in manufacturing and assessments of potency. Cytotherapy. 2019;21(3):289–306.
   PubMed Web of Science ®Google Scholar
• Sensebé L, Gadelorge M, Fleury-Cappellesso S. Production of mesenchymal stromal/stem cells according to good manufacturing practices: a review. Stem Cell Res Ther. 2013;4(3):66.
   PubMed Web of Science ®Google Scholar
• Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–833.
   PubMed Web of Science ®Google Scholar
• Galipeau J. The mesenchymal stromal cells dilemma‒does a negative phase III trial of random donor mesenchymal stromal cells in steroid-resistant graft-versus-host disease represent a death knell or a bump in the road? Cytotherapy. 2013;15(1):2–8.
   PubMed Web of Science ®Google Scholar