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Current Stem Cell Research & Therapy

Current Stem Cell Research & Therapy

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

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Research Article

Mesenchymal Stem Cells Target Gastric Cancer and Deliver Epirubicin via Tunneling Nanotubes for Enhanced Chemotherapy

Author(s): Yali Zhou, Yumin Li, Haibin Wang, Haolin Sun, Jing Su, Yaqiong Fan, Wei Xing and Jie Fu*

Volume 19, Issue 10, 2024

Published on: 03 January, 2024

Page: [1402 - 1413] Pages: 12

DOI: 10.2174/011574888X287102240101060146

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Abstract

Background: A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes.

Objective: Epirubicin delivery to gastric cancer cells using mesenchymal stem cells.

Methods: In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS.

Results: Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05).

Conclusions: We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

Keywords: Mesenchymal stem cell, tunneling nanotubes, targeted deliver, epirubicin, gastric cancer, chemotherapy effect.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. 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.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Shi, J.; Li, N.; Tang, Y.; Jiang, L.; Yang, L.; Wang, S.; Song, Y.; Liu, Y.; Fang, H.; Lu, N.; Qi, S.; Chen, B.; Li, Z.; Liu, S.; Wang, J.; Wang, W.; Zhu, S.; Yang, J.; Li, Y.; Zhao, D.; Jin, J. Total neoadjuvant therapy for locally advanced gastric cancer and esophagogastric junction adenocarcinoma: Study protocol for a prospective, multicenter, single-arm, phase II clinical trial. BMC Gastroenterol., 2022, 22(1), 359.
[http://dx.doi.org/10.1186/s12876-022-02440-5] [PMID: 35902798]
[3]
Printezi, M.I.; Kilgallen, A.B.; Bond, M.J.G.; Štibler, U.; Putker, M.; Teske, A.J.; Cramer, M.J.; Punt, C.J.A.; Sluijter, J.P.G.; Huitema, A.D.R.; May, A.M.; van Laake, L.W. Toxicity and efficacy of chronomodulated chemotherapy: A systematic review. Lancet Oncol., 2022, 23(3), e129-e143.
[http://dx.doi.org/10.1016/S1470-2045(21)00639-2] [PMID: 35240088]
[4]
Yang, H.; Xu, L.; Guan, S.; Hao, X.; Ge, Z.; Tong, F.; Cao, Y.; Liu, P.; Zhou, B.; Cheng, L.; Liu, M.; Liu, H.; Xie, F.; Wang, S.; Peng, Y.; Wang, C.; Wang, S. Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: An open-label, randomized, multi-center, phase II Trial. BMC Cancer, 2022, 22(1), 1357.
[http://dx.doi.org/10.1186/s12885-022-10439-0] [PMID: 36577958]
[5]
Jiali, Z; En, L; Chaonong, C Combined treatment of tanshinone I and epirubicin revealed enhanced inhibition of hepatocellular carcinoma by targeting PI3K/AKT/HIF-1α. Drug Des Devel Ther, 2022, 16, 3197-3213.
[6]
Li, X.; Guo, X.; Li, J.; Yuan, L.; Wang, H. Preventing effect of astragalus polysaccharide on cardiotoxicity induced by chemotherapy of epirubicin: A pilot study. Medicine, 2022, 101(32), e30000.
[http://dx.doi.org/10.1097/MD.0000000000030000] [PMID: 35960075]
[7]
Rosati, G.; Cella, C.A.; Cavanna, L.; Codecà, C.; Prisciandaro, M.; Mosconi, S.; Luchena, G.; Silvestris, N.; Bernardini, I.; Casaretti, R.; Zoratto, F.; Amoroso, D.; Ciarlo, A.; Barni, S.; Cascinu, S.; Davite, C.; Di Sanzo, A.; Casolaro, A.; Bilancia, D.; Labianca, R. A randomized phase III study of fractionated docetaxel, oxaliplatin, capecitabine (low-tox) vs epirubicin, oxaliplatin and capecitabine (eox) in patients with locally advanced unresectable or metastatic gastric cancer: The lega trial. Gastric Cancer, 2022, 25(4), 783-793.
[http://dx.doi.org/10.1007/s10120-022-01292-y] [PMID: 35352176]
[8]
Liu, K.; Song, J.; Yan, Y.; Zou, K.; Che, Y.; Wang, B.; Li, Z.; Yu, W.; Guo, W.; Zou, L.; Deng, W.; Sun, X. Melatonin increases the chemosensitivity of diffuse large B-cell lymphoma cells to epirubicin by inhibiting P-glycoprotein expression via the NF-κB pathway. Transl. Oncol., 2021, 14(1), 100876.
[http://dx.doi.org/10.1016/j.tranon.2020.100876] [PMID: 33007707]
[9]
Felipe, A.V.; Oliveira, J.; Moraes, A.A.; França, J.P.; Silva, T.D.; Forones, N.M. Reversal of multidrug resistance in an epirubicin-resistant gastric cancer cell subline. Asian Pac. J. Cancer Prev., 2018, 19(5), 1237-1242.
[PMID: 29801407]
[10]
Naji, A.; Eitoku, M.; Favier, B.; Deschaseaux, F.; Rouas-Freiss, N.; Suganuma, N. Biological functions of mesenchymal stem cells and clinical implications. Cell. Mol. Life Sci., 2019, 76(17), 3323-3348.
[http://dx.doi.org/10.1007/s00018-019-03125-1] [PMID: 31055643]
[11]
Friedenstein, A.J.; Chailakhjan, R.K.; Lalykina, K.S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif., 1970, 3(4), 393-403.
[http://dx.doi.org/10.1111/j.1365-2184.1970.tb00347.x] [PMID: 5523063]
[12]
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]
[13]
Song, Y.; Li, R.; Ye, M.; Pan, C.; Zheng, L.; Wang, Z.; Zhu, X. Differences in chemotaxis of human mesenchymal stem cells and cervical cancer cells. Apoptosis, 2022, 27(11-12), 840-851.
[http://dx.doi.org/10.1007/s10495-022-01749-6] [PMID: 35849265]
[14]
Whitehead, J.; Zhang, J.; Harvestine, J.N.; Kothambawala, A.; Liu, G.; Leach, J.K. Tunneling nanotubes mediate the expression of senescence markers in mesenchymal stem/stromal cell spheroids. Stem Cells, 2020, 38(1), 80-89.
[http://dx.doi.org/10.1002/stem.3056] [PMID: 31298767]
[15]
Wei, B.; Ji, M.; Lin, Y.; Wang, S.; Liu, Y.; Geng, R.; Hu, X.; Xu, L.; Li, Z.; Zhang, W.; Lu, J. Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo. Stem Cell Res. Ther., 2023, 14(1), 104.
[http://dx.doi.org/10.1186/s13287-023-03329-0] [PMID: 37101277]
[16]
Paliwal, S.; Chaudhuri, R.; Agrawal, A.; Mohanty, S. Human tissue-specific MSCs demonstrate differential mitochondria transfer abilities that may determine their regenerative abilities. Stem Cell Res. Ther., 2018, 9(1), 298.
[http://dx.doi.org/10.1186/s13287-018-1012-0] [PMID: 30409230]
[17]
Krešić, N.; Prišlin, M.; Vlahović, D.; Kostešić, P.; Ljolje, I.; Brnić, D.; Turk, N.; Musulin, A.; Habrun, B. The expression pattern of surface markers in canine adipose-derived mesenchymal stem cells. Int. J. Mol. Sci., 2021, 22(14), 7476.
[http://dx.doi.org/10.3390/ijms22147476] [PMID: 34299095]
[18]
Lan, T.; Luo, M.; Wei, X. Mesenchymal stem/stromal cells in cancer therapy. J. Hematol. Oncol., 2021, 14(1), 195.
[http://dx.doi.org/10.1186/s13045-021-01208-w] [PMID: 34789315]
[19]
Meza-León, B.; Gratzinger, D.; Aguilar-Navarro, A.G.; Juárez-Aguilar, F.G.; Rebel, V.I.; Torlakovic, E.; Purton, L.E.; Dorantes-Acosta, E.M.; Escobar-Sánchez, A.; Dick, J.E.; Flores-Figueroa, E. Human, mouse, and dog bone marrow show similar mesenchymal stromal cells within a distinctive microenvironment. Exp. Hematol., 2021, 100, 41-51.
[http://dx.doi.org/10.1016/j.exphem.2021.06.006] [PMID: 34228982]
[20]
Zhang, H.; Qian, J.; Jin, M.; Fan, L.; Fan, S.; Pan, H.; Li, Y.; Wang, N.; Jian, B. Jolkinolide B induces cell cycle arrest and apoptosis in MKN45 gastric cancer cells and inhibits xenograft tumor growth in vivo. Biosci. Rep., 2022, 42(6), BSR20220341.
[http://dx.doi.org/10.1042/BSR20220341] [PMID: 35674158]
[21]
Chu, Y.; Xiao, Z.; Jing, N.; Yan, W.; Wang, S.; Ma, B.; Zhang, J.; Li, Y. Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells. Invest. New Drugs, 2021, 39(3), 627-635.
[http://dx.doi.org/10.1007/s10637-020-01016-y] [PMID: 33215324]
[22]
Shi, W.; Zhang, G.; Ma, Z.; Li, L.; Liu, M.; Qin, L.; Yu, Z.; Zhao, L.; Liu, Y.; Zhang, X.; Qin, J.; Ye, H.; Jiang, X.; Zhou, H.; Sun, H.; Jiao, Z. Hyperactivation of HER2-SHCBP1- PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer. Nat. Commun., 2021, 12(1), 2812.
[http://dx.doi.org/10.1038/s41467-021-23053-8] [PMID: 33990570]
[23]
Mick, A.P.; David, M.S.P.; Nicholas, H. Microscope-Cockpit: Python-based bespoke microscopy for bio-medical science. Wellcome Open Res, 2022, 6, 76.
[http://dx.doi.org/10.12688/wellcomeopenres.16610.1]
[24]
Feldman, D.; Singh, A.; Schmid-Burgk, J.L.; Carlson, R.J.; Mezger, A.; Garrity, A.J.; Zhang, F.; Blainey, P.C. Optical pooled screens in human cells. Cell, 2019, 179(3), 787-799.e17.
[http://dx.doi.org/10.1016/j.cell.2019.09.016] [PMID: 31626775]
[25]
Cromwell, E.F.; Leung, M.; Hammer, M.; Thai, A.; Rajendra, R.; Sirenko, O. Disease modeling with 3D cell-based assays using a novel flowchip system and high-content imaging. SLAS Technol., 2021, 26(3), 237-248.
[http://dx.doi.org/10.1177/24726303211000688] [PMID: 33783259]
[26]
Gregory, PW; Heba, S; Steven, S Evolution and impact of high content imaging. SLAS Discov, 2023, 3, S2472.
[http://dx.doi.org/10.1016/j.slasd.2023.08.009]
[27]
Coste, A.; Oktay, M.H.; Condeelis, J.S.; Entenberg, D. Intravital imaging techniques for biomedical and clinical research. Cytometry A, 2020, 97(5), 448-457.
[http://dx.doi.org/10.1002/cyto.a.23963] [PMID: 31889408]
[28]
Justus, C.R.; Marie, M.A.; Sanderlin, E.J.; Yang, L.V. Transwell in vitro cell migration and invasion assays. Methods Mol. Biol., 2023, 2644, 349-359.
[http://dx.doi.org/10.1007/978-1-0716-3052-5_22] [PMID: 37142933]
[29]
Marescotti, D.; Bovard, D.; Morelli, M.; Sandoz, A.; Luettich, K.; Frentzel, S.; Peitsch, M.; Hoeng, J. In vitro high-content imaging-based phenotypic analysis of bronchial 3D organotypic air-liquid interface cultures. SLAS Technol., 2020, 25(3), 247-252.
[http://dx.doi.org/10.1177/2472630319895473] [PMID: 31971054]
[30]
Guo, Z.; Cui, Z. Fluorescent nanotechnology for in vivo imaging. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2021, 13(5), e1705.
[http://dx.doi.org/10.1002/wnan.1705] [PMID: 33686803]
[31]
Kalimuthu, S.; Zhu, L.; Oh, J.M.; Gangadaran, P.; Lee, H.W.; Baek, S.; Rajendran, R.L.; Gopal, A.; Jeong, S.Y.; Lee, S.W.; Lee, J.; Ahn, B.C. Migration of mesenchymal stem cells to tumor xenograft models and in vitro drug delivery by doxorubicin. Int. J. Med. Sci., 2018, 15(10), 1051-1061.
[http://dx.doi.org/10.7150/ijms.25760] [PMID: 30013447]
[32]
Saha, T.; Dash, C.; Jayabalan, R.; Khiste, S.; Kulkarni, A.; Kurmi, K.; Mondal, J.; Majumder, P.K.; Bardia, A.; Jang, H.L.; Sengupta, S. Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells. Nat. Nanotechnol., 2022, 17(1), 98-106.
[http://dx.doi.org/10.1038/s41565-021-01000-4] [PMID: 34795441]
[33]
Pacioni, S.; D’Alessandris, Q.G.; Giannetti, S.; Morgante, L.; De Pascalis, I.; Coccè, V.; Bonomi, A.; Pascucci, L.; Alessandri, G.; Pessina, A.; Falchetti, M.L.; Pallini, R. Mesenchymal stromal cells loaded with paclitaxel induce cytotoxic damage in glioblastoma brain xenografts. Stem Cell Res. Ther., 2015, 6(1), 194.
[http://dx.doi.org/10.1186/s13287-015-0185-z] [PMID: 26445228]
[34]
Luo, Y.; Fu, X.; Han, B.; Zhang, F.; Yuan, L.; Men, H.; Zhang, S.; Tian, S.; Dong, B.; Meng, M. The apoptosis mechanism of epirubicin combined with bcg on human bladder cancer cells. Anticancer. Agents Med. Chem., 2020, 20(13), 1571-1581.
[http://dx.doi.org/10.2174/1871520620666200502004002] [PMID: 32357825]
[35]
Victor, AH; Jessika, CM; Xinyi, W Use of CRISPR/Cas9 with homology-directed repair to silence the human topoisomerase IIα intron-19 5' splice site: Generation of etoposide resistance in human leukemia K562 cells. PLoS One, 2022, 175, e0265794.
[36]
Inès, L; Eléonore, S Pembrolizumab with trastuzumab and chemotherapy-advanced or metastatic gastric or gastro-esophageal junction adenocarcinomas with surexpression of HER2 and CPS≥1. Bull Cancer, 2023, 8, S0007.
[http://dx.doi.org/10.1016/j.bulcan.2023.11.004]
[37]
Al-Batran, S.E.; Homann, N.; Pauligk, C.; Goetze, T.O.; Meiler, J.; Kasper, S.; Kopp, H.G.; Mayer, F.; Haag, G.M.; Luley, K.; Lindig, U.; Schmiegel, W.; Pohl, M.; Stoehlmacher, J.; Folprecht, G.; Probst, S.; Prasnikar, N.; Fischbach, W.; Mahlberg, R.; Trojan, J.; Koenigsmann, M.; Martens, U.M.; Thuss-Patience, P.; Egger, M.; Block, A.; Heinemann, V.; Illerhaus, G.; Moehler, M.; Schenk, M.; Kullmann, F.; Behringer, D.M.; Heike, M.; Pink, D.; Teschendorf, C.; Löhr, C.; Bernhard, H.; Schuch, G.; Rethwisch, V.; von Weikersthal, L.F.; Hartmann, J.T.; Kneba, M.; Daum, S.; Schulmann, K.; Weniger, J.; Belle, S.; Gaiser, T.; Oduncu, F.S.; Güntner, M.; Hozaeel, W.; Reichart, A.; Jäger, E.; Kraus, T.; Mönig, S.; Bechstein, W.O.; Schuler, M.; Schmalenberg, H.; Hofheinz, R.D. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet, 2019, 393(10184), 1948-1957.
[http://dx.doi.org/10.1016/S0140-6736(18)32557-1] [PMID: 30982686]
[38]
Ansaar, R.; Meech, R.; Rowland, A. A physiologically based pharmacokinetic model to predict determinants of variability in epirubicin exposure and tissue distribution. Pharmaceutics, 2023, 15(4), 1222.
[http://dx.doi.org/10.3390/pharmaceutics15041222] [PMID: 37111707]
[39]
Isemede, D.A.; Sharma, A.; Bailey, J. Assessing the cardiotoxicity of Epirubicin-based chemotherapy in patients with breast cancer using high-sensitivity cardiac troponin T, N-terminal pro b-type natriuretic peptide and soluble suppression of tumorigenicity-2. Ann. Clin. Biochem., 2022, 59(6), 410-419.
[http://dx.doi.org/10.1177/00045632221131672] [PMID: 36154484]
[40]
Deniz, I.A.; Karbanová, J.; Wobus, M.; Bornhäuser, M.; Wimberger, P.; Kuhlmann, J.D.; Corbeil, D. Mesenchymal stromal cell-associated migrasomes: A new source of chemoattractant for cells of hematopoietic origin. Cell Commun. Signal., 2023, 21(1), 36.
[http://dx.doi.org/10.1186/s12964-022-01028-6] [PMID: 36788616]
[41]
Ullah, M.; Liu, D.D.; Thakor, A.S. Mesenchymal stromal cell homing: Mechanisms and strategies for improvement. iScience, 2019, 15, 421-438.
[http://dx.doi.org/10.1016/j.isci.2019.05.004] [PMID: 31121468]
[42]
Sergey, T; Natalya, MD; Peter, ST To explore the stem cells homing to GBM: The rise to the occasion. Biomedicines, 2022, 10(5), 986.
[43]
Zhang, N.; Song, Y.; Huang, Z.; Chen, J.; Tan, H.; Yang, H.; Fan, M.; Li, Q.; Wang, Q.; Gao, J.; Pang, Z.; Qian, J.; Ge, J. Monocyte mimics improve mesenchymal stem cell-derived extracellular vesicle homing in a mouse MI/RI model. Biomaterials, 2020, 255, 120168.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120168] [PMID: 32562944]
[44]
Szydlak, R. Biological, chemical and mechanical factors regulating migration and homing of mesenchymal stem cells. World J. Stem Cells, 2021, 13(6), 619-631.
[http://dx.doi.org/10.4252/wjsc.v13.i6.619] [PMID: 34249231]
[45]
Yuan, M.; Hu, X.; Yao, L.; Jiang, Y.; Li, L. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease. Stem Cell Res. Ther., 2022, 13(1), 179.
[http://dx.doi.org/10.1186/s13287-022-02858-4] [PMID: 35505419]
[46]
Zheng, X.B.; He, X.W.; Zhang, L.J.; Qin, H.B.; Lin, X.T.; Liu, X.H.; Zhou, C.; Liu, H.S.; Hu, T.; Cheng, H.C.; He, X.S.; Wu, X.R.; Chen, Y.F.; Ke, J.; Wu, X.J.; Lan, P. Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice. Gastroenterol. Rep., 2019, 7(2), 127-138.
[http://dx.doi.org/10.1093/gastro/goy017] [PMID: 30976426]
[47]
a) Laurent, MCG; Olivier, DW; José, AG Cell line derived xenograft mouse models are a suitable in vivo model for studying tumor budding in colorectal cancer. Front Med, 2019, 27(6), 139.
[http://dx.doi.org/10.3389/fmed.2019.00139];
b) Chiara, Z. Tunneling nanotubes: Reshaping connectivi-ty. Curr Opin Cell Biol, 2021, 71, 139-147.
[48]
Takayama, Y.; Kusamori, K.; Tsukimori, C.; Shimizu, Y.; Hayashi, M.; Kiyama, I.; Katsumi, H.; Sakane, T.; Yamamoto, A.; Nishikawa, M. Anticancer drug-loaded mesenchymal stem cells for targeted cancer therapy. J. Control. Release, 2021, 329, 1090-1101.
[http://dx.doi.org/10.1016/j.jconrel.2020.10.037] [PMID: 33098911]
[49]
Luchetti, F.; Carloni, S.; Nasoni, M.G.; Reiter, R.J.; Balduini, W. Tunneling nanotubes and mesenchymal stem cells: New insights into the role of melatonin in neuronal recovery. J. Pineal Res., 2022, 73(1), e12800.
[http://dx.doi.org/10.1111/jpi.12800] [PMID: 35419879]
[50]
Hase, K.; Kimura, S.; Takatsu, H.; Ohmae, M.; Kawano, S.; Kitamura, H.; Ito, M.; Watarai, H.; Hazelett, C.C.; Yeaman, C.; Ohno, H. M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex. Nat. Cell Biol., 2009, 11(12), 1427-1432.
[http://dx.doi.org/10.1038/ncb1990] [PMID: 19935652]
[51]
Chauveau, A.; Aucher, A.; Eissmann, P.; Vivier, E.; Davis, D.M. Membrane nanotubes facilitate long-distance interactions between natural killer cells and target cells. Proc. Natl. Acad. Sci., 2010, 107(12), 5545-5550.
[http://dx.doi.org/10.1073/pnas.0910074107] [PMID: 20212116]
[52]
Pinto, G.; Saenz-de-Santa-Maria, I.; Chastagner, P.; Perthame, E.; Delmas, C.; Toulas, C.; Moyal-Jonathan-Cohen, E.; Brou, C.; Zurzolo, C. Patient-derived glioblastoma stem cells transfer mitochondria through tunneling nanotubes in tumor organoids. Biochem. J., 2021, 478(1), 21-39.
[http://dx.doi.org/10.1042/BCJ20200710] [PMID: 33245115]
[53]
Burt, R.; Dey, A.; Aref, S.; Aguiar, M.; Akarca, A.; Bailey, K.; Day, W.; Hooper, S.; Kirkwood, A.; Kirschner, K.; Lee, S.W.; Lo Celso, C.; Manji, J.; Mansour, M.R.; Marafioti, T.; Mitchell, R.J.; Muirhead, R.C.; Cheuk Yan Ng, K.; Pospori, C.; Puccio, I.; Zuborne-Alapi, K.; Sahai, E.; Fielding, A.K. Activated stromal cells transfer mitochondria to rescue acute lymphoblastic leukemia cells from oxidative stress. Blood, 2019, 134(17), 1415-1429.
[http://dx.doi.org/10.1182/blood.2019001398] [PMID: 31501154]
[54]
Feng, Y.; Zhu, R.; Shen, J.; Wu, J.; Lu, W.; Zhang, J.; Zhang, J.; Liu, K. Human bone marrow mesenchymal stem cells rescue endothelial cells experiencing chemotherapy stress by mitochondrial transfer via tunneling nanotubes. Stem Cells Dev., 2019, 28(10), 674-682.
[http://dx.doi.org/10.1089/scd.2018.0248] [PMID: 30808254]
[55]
Holstein, S.A.; Lunning, M.A. CAR T-cell therapy in hematologic malignancies: A voyage in progress. Clin. Pharmacol. Ther., 2020, 107(1), 112-122.
[http://dx.doi.org/10.1002/cpt.1674] [PMID: 31622496]
[56]
Xiaomin, Z; Lingling, Z; Hui, Z CAR-T cell therapy in hematological malignancies: Current opportunities and challenges. Front Immunol, 2022, 13, 927153.
[http://dx.doi.org/10.3389/fimmu.2022.927153]
[57]
Haslauer, T.; Greil, R.; Zaborsky, N.; Geisberger, R. CAR T-cell therapy in hematological malignancies. Int. J. Mol. Sci., 2021, 22(16), 8996.
[http://dx.doi.org/10.3390/ijms22168996] [PMID: 34445701]
[58]
Wagner, J.; Wickman, E.; DeRenzo, C.; Gottschalk, S. CAR T cell therapy for solid tumors: Bright future or dark reality? Mol. Ther., 2020, 28(11), 2320-2339.
[http://dx.doi.org/10.1016/j.ymthe.2020.09.015] [PMID: 32979309]
[59]
Ma, S.; Li, X.; Wang, X.; Cheng, L.; Li, Z.; Zhang, C.; Ye, Z.; Qian, Q. Current progress in CAR-T cell therapy for solid tumors. Int. J. Biol. Sci., 2019, 15(12), 2548-2560.
[http://dx.doi.org/10.7150/ijbs.34213] [PMID: 31754328]
[60]
Maalej, K.M.; Merhi, M.; Inchakalody, V.P.; Mestiri, S.; Alam, M.; Maccalli, C.; Cherif, H.; Uddin, S.; Steinhoff, M.; Marincola, F.M.; Dermime, S. CAR-cell therapy in the era of solid tumor treatment: Current challenges and emerging therapeutic advances. Mol. Cancer, 2023, 22(1), 20.
[http://dx.doi.org/10.1186/s12943-023-01723-z] [PMID: 36717905]
[61]
Duan, H.; Liu, C.; Hou, Y.; Liu, Y.; Zhang, Z.; Zhao, H.; Xin, X.; Liu, W.; Zhang, X.; Chen, L.; Jin, M.; Gao, Z.; Huang, W. Sequential delivery of quercetin and paclitaxel for the fibrotic tumor microenvironment remodeling and chemotherapy potentiation via a dual-targeting hybrid micelle-in-liposome system. ACS Appl. Mater. Interfaces, 2022, 14(8), 10102-10116.
[http://dx.doi.org/10.1021/acsami.1c23166] [PMID: 35175043]
[62]
Nguyen, D.T.; Ogando-Rivas, E.; Liu, R.; Wang, T.; Rubin, J.; Jin, L.; Tao, H.; Sawyer, W.W.; Mendez-Gomez, H.R.; Cascio, M.; Mitchell, D.A.; Huang, J.; Sawyer, W.G.; Sayour, E.J.; Castillo, P. CAR T cell locomotion in solid tumor microenvironment. Cells, 2022, 11(12), 1974.
[http://dx.doi.org/10.3390/cells11121974] [PMID: 35741103]
[63]
Arneth, B. Tumor microenvironment. Medicina, 2019, 56(1), 15.
[http://dx.doi.org/10.3390/medicina56010015] [PMID: 31906017]
[64]
Martinez, M.; Moon, E.K. CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front. Immunol., 2019, 10, 128.
[http://dx.doi.org/10.3389/fimmu.2019.00128] [PMID: 30804938]
[65]
Marofi, F.; Motavalli, R.; Safonov, V.A.; Thangavelu, L.; Yumashev, A.V.; Alexander, M.; Shomali, N.; Chartrand, M.S.; Pathak, Y.; Jarahian, M.; Izadi, S.; Hassanzadeh, A.; Shirafkan, N.; Tahmasebi, S.; Khiavi, F.M. CAR T cells in solid tumors: Challenges and opportunities. Stem Cell Res. Ther., 2021, 12(1), 81.
[http://dx.doi.org/10.1186/s13287-020-02128-1] [PMID: 33494834]
[66]
Lin, Y.T.; Zheng, X.Y.; Yao, Y.F.; Zhang, Y.Y.; Huang, T.T.; Zhu, Y.L.; Pei, J.; Wang, J.; Chu, M.; Wang, Y.D. [Therapeutic effect of spleen low molecular weight extracts on leukopenia caused by epirubicin in mice and its mechanism]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2021, 29(3), 969-974.
[http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.03.050] [PMID: 34105502]
[67]
de la Hoz-Camacho, R.; Rivera-Lazarín, A.L.; Vázquez-Guillen, J.M.; Caballero-Hernández, D.; Mendoza-Gamboa, E.; Martínez-Torres, A.C.; Rodríguez-Padilla, C. Cyclophosphamide and epirubicin induce high apoptosis in microglia cells while epirubicin provokes DNA damage and microglial activation at sub-lethal concentrations. EXCLI J., 2022, 21(21), 197-212.
[http://dx.doi.org/10.17179/excli2021-4160] [PMID: 35145370]
[68]
Haroon, H.B.; Hunter, A.C.; Farhangrazi, Z.S.; Moghimi, S.M. A brief history of long circulating nanoparticles. Adv. Drug Deliv. Rev., 2022, 188, 114396.
[http://dx.doi.org/10.1016/j.addr.2022.114396] [PMID: 35798129]
[69]
Niu, Y.D.; Zhang, Y.W.; Zhu, R.J.; Chu, T.; Wang, L.; Wang, S.; Li, Y.Y.; Dong, Y. [The influence of various myelosuppression degrees during neoadjuvant chemotherapy on the curative effect and prognosis of triple-negative breast cancer]. Zhonghua Yi Xue Za Zhi, 2022, 102(29), 2290-2294.
[PMID: 35927061]
[70]
Luan, X.D.; Zhao, K.H.; Hou, H.; Gai, Y.H.; Wang, Q.T.; Mu, Q.; Wan, Y. Changes in ischemia-modified albumin in myocardial toxicity induced by anthracycline and docetaxel chemotherapy. Medicine, 2017, 96(32), e7681.
[http://dx.doi.org/10.1097/MD.0000000000007681] [PMID: 28796051]
[71]
Roberts, R.; Hanna, L.; Borley, A.; Dolan, G.; Williams, E.M. Epirubicin chemotherapy in women with breast cancer: Alternating arms for intravenous administration to reduce chemical phlebitis. Eur. J. Cancer Care, 2019, 28(5), e13114.
[http://dx.doi.org/10.1111/ecc.13114] [PMID: 31148328]
[72]
Song, N.; Scholtemeijer, M.; Shah, K. Mesenchymal stem cell immunomodulation: Mechanisms and therapeutic potential. Trends Pharmacol. Sci., 2020, 41(9), 653-664.
[http://dx.doi.org/10.1016/j.tips.2020.06.009] [PMID: 32709406]
[73]
Hu, C.; Li, L. The immunoregulation of mesenchymal stem cells plays a critical role in improving the prognosis of liver transplantation. J. Transl. Med., 2019, 17(1), 412.
[http://dx.doi.org/10.1186/s12967-019-02167-0] [PMID: 31823784]
[74]
de Wolf, C.; van de Bovenkamp, M.; Hoefnagel, M. Regulatory perspective on in vitro potency assays for human mesenchymal stromal cells used in immunotherapy. Cytotherapy, 2017, 19(7), 784-797.
[http://dx.doi.org/10.1016/j.jcyt.2017.03.076] [PMID: 28457740]
[75]
Huang, Y.; Wu, Q.; Tam, P.K.H. Immunomodulatory mechanisms of mesenchymal stem cells and their potential clinical applications. Int. J. Mol. Sci., 2022, 23(17), 10023.
[http://dx.doi.org/10.3390/ijms231710023] [PMID: 36077421]

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