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

  • Authors: Zhou Y.1, Li Y.2, Wang H.1, Sun H.3, Su J.1, Fan Y.1, Xing W.4, Fu J.5
  • Affiliations:
    1. Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University
    2. Key Laboratory of Digestive System Tumors of Gansu Province, The Second Hospital & Clinical Medical School, Lanzhou University
    3. Cuiying Biomedical Research Center, The Second Clinical College of Lanzhou University
    4. Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University,
    5. Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University
  • Issue: Vol 19, No 10 (2024)
  • Pages: 1402-1413
  • Section: Medicine
  • URL: https://rjpbr.com/1574-888X/article/view/645499
  • DOI: https://doi.org/10.2174/011574888X287102240101060146
  • ID: 645499

Cite item

Full Text

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.

About the authors

Yali Zhou

Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University

Email: info@benthamscience.net

Yumin Li

Key Laboratory of Digestive System Tumors of Gansu Province, The Second Hospital & Clinical Medical School, Lanzhou University

Email: info@benthamscience.net

Haibin Wang

Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University

Email: info@benthamscience.net

Haolin Sun

Cuiying Biomedical Research Center, The Second Clinical College of Lanzhou University

Email: info@benthamscience.net

Jing Su

Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University

Email: info@benthamscience.net

Yaqiong Fan

Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University

Email: info@benthamscience.net

Wei Xing

Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University,

Email: info@benthamscience.net

Jie Fu

Department of General Surgery, The Second Hospital & Clinical Medical School, Lanzhou University

Author for correspondence.
Email: info@benthamscience.net

References

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1177/24726303211000688 PMID: 33783259
  26. Gregory, PW; Heba, S; Steven, S Evolution and impact of high content imaging. SLAS Discov, 2023, 3, S2472. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.3390/cells11121974 PMID: 35741103
  63. Arneth, B. Tumor microenvironment. Medicina, 2019, 56(1), 15. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.3390/ijms231710023 PMID: 36077421

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers