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BioMed Research International
Volume 2019, Article ID 2820853, 12 pages
https://doi.org/10.1155/2019/2820853
Review Article

Mesenchymal Stem Cells and Cancer: Clinical Challenges and Opportunities

1Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
2Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
3Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
4Laboratory of Orthopaedics & Traumatology, Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China

Correspondence should be addressed to Gang Li; kh.ude.khuc@ilgnag, Leilei Chen; moc.anis@0101_naituy, and Liangliang Xu; nc.ude.mcuzg@6102-llux

Received 31 December 2018; Revised 19 March 2019; Accepted 10 April 2019; Published 8 May 2019

Academic Editor: Martin Bornhäuser

Copyright © 2019 Weiping Lin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. J. Friedenstein, “Precursor cells of mechanocytes,” International Review of Cytology-A Survey Of Cell Biology, vol. 47, pp. 327–359, 1976. View at Publisher · View at Google Scholar · View at Scopus
  2. A. J. Friedenstein, R. K. Chailakhjan, and K. S. Lalykina, “The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells,” Cell Tissue Kinet, vol. 3, no. 4, pp. 393–403, 1970. View at Publisher · View at Google Scholar · View at Scopus
  3. M. B. Murphy, K. Moncivais, and A. I. Caplan, “Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine,” Experimental & Molecular Medicine, vol. 45, no. 11, article e54, 2013. View at Publisher · View at Google Scholar · View at Scopus
  4. P. A. Zuk, M. Zhu, H. Mizuno et al., “Multilineage cells from human adipose tissue: implications for cell-based therapies,” Tissue Engineering Part A, vol. 7, no. 2, pp. 211–228, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. J. J. Minguell, A. Erices, and P. Conget, “Mesenchymal stem cells,” Experimental Biology and Medicine, vol. 226, no. 6, pp. 507–520, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. C. Nombela-Arrieta, J. Ritz, and L. E. Silberstein, “The elusive nature and function of mesenchymal stem cells,” Nature Reviews Molecular Cell Biology, vol. 12, no. 2, pp. 126–131, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Dominici, K. Le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. the international society for cellular therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. Y. Wang, X. Chen, W. Cao, and Y. Shi, “Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications,” Nature Immunology, vol. 15, no. 11, pp. 1009–1016, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. J. A. Ankrum, J. F. Ong, and J. M. Karp, “Mesenchymal stem cells: immune evasive, not immune privileged,” Nature Biotechnology, vol. 32, no. 3, pp. 252–260, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. J. P. A. Gomes, A. F. Assoni, M. Pelatti, G. Coatti, S. K. Okamoto, and M. Zatz, “Deepening a simple question: Can MSCs be used to treat cancer?” Anticancer Reseach, vol. 37, no. 9, pp. 4747–4758, 2017. View at Publisher · View at Google Scholar · View at Scopus
  11. R. S. Y. Wong, “Mesenchymal stem cells: angels or demons?” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 459510, 8 pages, 2011. View at Publisher · View at Google Scholar
  12. T. Liu, K. Zhu, C. Ke et al., “Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model,” American Journal of Translational Research, vol. 9, no. 6, pp. 2891–2900, 2017. View at Google Scholar
  13. Y. Yulyana, I. A. W. Ho, K. C. Sia et al., “Paracrine factors of human fetal MSCs inhibit liver cancer growth through reduced activation of IGF-1R/PI3K/Akt signaling,” Molecular Therapy, vol. 23, no. 4, pp. 746–756, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. S. Kidd, L. Caldwell, M. Dietrich et al., “Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment,” Cytotherapy, vol. 12, no. 5, pp. 615–625, 2010. View at Publisher · View at Google Scholar
  15. S. M. Albarenque, R. M. Zwacka, and A. Mohr, “Both human and mouse mesenchymal stem cells promote breast cancer metastasis,” Stem Cell Research, vol. 7, no. 2, pp. 163–171, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. K. Shinagawa, Y. Kitadai, M. Tanaka et al., “Mesenchymal stem cells enhance growth and metastasis of colon cancer,” International Journal of Cancer, vol. 127, no. 10, pp. 2323–2333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. P. Chaturvedi, D. M. Gilkes, C. C. Wong et al., “Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis,” The Journal of Clinical Investigation, vol. 123, no. 1, pp. 189–205, 2013. View at Publisher · View at Google Scholar
  18. W. Zhong, Y. Tong, Y. Li et al., “Mesenchymal stem cells in inflammatory microenvironment potently promote metastatic growth of cholangiocarcinoma via activating Akt/NF-kappaB signaling by paracrine CCL5,” Oncotarget, vol. 8, no. 43, pp. 73693–73704, 2017. View at Google Scholar · View at Scopus
  19. R. Lee, N. Yoon, J. Reneau, and D. Prockop, “Preactivation of human MSCs with TNF-alpha enhances tumor-suppressive activity,” Cell Stem Cell, vol. 11, no. 6, pp. 825–835, 2012. View at Publisher · View at Google Scholar
  20. S. François, B. Usunier, M. Forgue-Lafitte et al., “Mesenchymal stem cell administration attenuates colon cancer progression by modulating the immune component within the colorectal tumor microenvironment,” Stem Cells Translational Medicine, vol. 8, no. 3, pp. 285–300, 2019. View at Publisher · View at Google Scholar
  21. M. Walter, S. Liang, S. Ghosh, P. J. Hornsby, and R. Li, “Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells,” Oncogene, vol. 28, no. 30, pp. 2745–2755, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. K. S. Tsai, S. H. Yang, Y. P. Lei et al., “Mesenchymal stem cells promote formation of colorectal tumors in mice,” Gastroenterology, vol. 141, no. 3, pp. 1046–1056, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Zhang, Y. W. Lee, Y. F. Rui, T. Y. Cheng, X. H. Jiang, and G. Li, “Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors,” Stem Cell Research & Therapy, vol. 4, no. 3, article 70, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. C. P. El-Haibi, G. W. Bell, J. Zhang et al., “Critical role for lysyl oxidase in mesenchymal stem cell-driven breast cancer malignancy,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 109, no. 43, pp. 17460–17465, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. S. A. Patel, J. R. Meyer, S. J. Greco, K. E. Corcoran, M. Bryan, and P. Rameshwar, “Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-beta,” The Journal of Immunology, vol. 184, no. 10, pp. 5885–5894, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. E. M. Chandler, B. R. Seo, J. P. Califano et al., “Implanted adipose progenitor cells as physicochemical regulators of breast cancer,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 109, no. 25, pp. 9786–9791, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. M. E. Gonzalez, E. E. Martin, T. Anwar et al., “Mesenchymal stem cell-induced DDR2 mediates stromal-breast cancer interactions and metastasis growth,” Cell Reports, vol. 18, no. 5, pp. 1215–1228, 2017. View at Publisher · View at Google Scholar · View at Scopus
  28. I. A. W. Ho, H. C. Toh, W. H. Ng et al., “Human bone marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesis,” Stem Cells, vol. 31, no. 1, pp. 146–155, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Leng, Y. Wang, N. He et al., “Molecular imaging for assessment of mesenchymal stem cells mediated breast cancer therapy,” Biomaterials, vol. 35, no. 19, pp. 5162–5170, 2014. View at Publisher · View at Google Scholar · View at Scopus
  30. A. V. Meleshina, E. I. Cherkasova, M. V. Shirmanova et al., “Influence of mesenchymal stem cells on metastasis development in mice in vivo,” Stem Cell Research & Therapy, vol. 6, no. 1, 2015. View at Google Scholar · View at Scopus
  31. V. R. Dasari, K. Kaur, K. K. Velpula et al., “Upregulation of PTEN in Glioma Cells by Cord Blood Mesenchymal Stem Cells Inhibits Migration via Downregulation of the PI3K/Akt Pathway,” PLoS ONE, vol. 5, no. 4, Article ID e10350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Xie, D.-Y. Xie, B.-L. Lin et al., “Interferon-beta gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway,” British Journal of Cancer, vol. 109, no. 5, pp. 1198–1205, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. N. Wu, Y. L. Zhang, H. T. Wang et al., “Overexpression of hepatocyte nuclear factor 4 alpha in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/beta-catenin signaling pathway downregulation,” Cancer Biology & Therapy, vol. 17, no. 5, pp. 558–565, 2016. View at Google Scholar
  34. D. Chen, Y. Sun, Y. Yuan et al., “miR-100 induces epithelial-mesenchymal transition but suppresses tumorigenesis, migration and invasion,” PLoS Genetics, vol. 10, no. 2, Article ID e1004177, 2014. View at Publisher · View at Google Scholar
  35. K. Pakravan, S. Babashah, M. Sadeghizadeh et al., “MicroRNA-100 shuttled by mesenchymal stem cell-derived exosomes suppresses in vitro angiogenesis through modulating the mTOR/HIF-1alpha/VEGF signaling axis in breast cancer cells,” Cellular Oncology, vol. 40, no. 5, pp. 457–470, 2017. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Li and F. Li, “Exosomes from BM-MSCs increase the population of CSCs via transfer of miR-142-3p,” British Journal of Cancer, vol. 119, no. 6, pp. 744–755, 2018. View at Publisher · View at Google Scholar · View at Scopus
  37. A. M. Roccaro, A. Sacco, P. Maiso et al., “BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression,” The Journal of Clinical Investigation, vol. 123, no. 4, pp. 1542–1555, 2013. View at Publisher · View at Google Scholar · View at Scopus
  38. Y. Zhang, W. Dong, J. Wang, J. Cai, and Z. Wang, “Human omental adipose-derived mesenchymal stem cell-conditioned medium alters the proteomic profile of epithelial ovarian cancer cell lines in vitro,” OncoTargets and Therapy, vol. 10, pp. 1655–1663, 2017. View at Publisher · View at Google Scholar · View at Scopus
  39. W. Wang, W. Zhong, J. Yuan et al., “Involvement of Wnt/beta-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma,” Oncotarget, vol. 6, no. 39, pp. 42276–42289, 2015. View at Google Scholar · View at Scopus
  40. H. D. Lin, C.-Y. Fong, A. Biswas, M. Choolani, and A. Bongso, “Human umbilical cord wharton's jelly stem cell conditioned medium induces tumoricidal effects on lymphoma cells through hydrogen peroxide mediation,” Journal of Cellular Biochemistry, vol. 117, no. 9, pp. 2045–2055, 2016. View at Publisher · View at Google Scholar · View at Scopus
  41. R. Ramasamy, E. W. Lam, I. Soeiro, V. Tisato, D. Bonnet, and F. Dazzi, “Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth,” Leukemia, vol. 21, no. 2, pp. 304–310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. E. L. Spaeth, J. L. Dembinski, A. K. Sasser et al., “Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression,” PLoS ONE, vol. 4, no. 4, Article ID e4992, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Bexell, S. Gunnarsson, A. Tormin et al., “Bone marrow multipotent mesenchymal stroma cells act as pericyte-like migratory vehicles in experimental gliomas,” Molecular Therapy: The Journal of the American Society of Gene Therapy, vol. 17, no. 1, pp. 183–190, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Dong, Y. Pu, L. Zhang et al., “Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410,” Cell Death & Disease, vol. 9, no. 2, p. 218, 2018. View at Publisher · View at Google Scholar
  45. M. Wang, C. Zhao, H. Shi et al., “Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer,” British Journal of Cancer, vol. 110, no. 5, pp. 1199–1210, 2014. View at Publisher · View at Google Scholar
  46. K. Nakamura, Y. Ito, Y. Kawano et al., “Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model,” Gene Therapy, vol. 11, no. 14, pp. 1155–1164, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Qiao, W. Xu, W. Zhu et al., “Human mesenchymal stem cells isolated from the umbilical cord,” Cell Biology International, vol. 32, no. 1, pp. 8–15, 2008. View at Google Scholar
  48. L. Qiao, Z. Xu, T. Zhao et al., “Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model,” Cell Research, vol. 18, no. 4, pp. 500–507, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Otsu, S. Das, S. D. Houser, S. K. Quadri, S. Bhattacharya, and J. Bhattacharya, “Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells,” Blood, vol. 113, no. 18, pp. 4197–4205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. A. Y. Khakoo, S. Pati, S. A. Anderson et al., “Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma,” The Journal of Experimental Medicine, vol. 203, no. 5, pp. 1235–1247, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. A. F. Chambers, A. C. Groom, and I. C. MacDonald, “Dissemination and growth of cancer cells in metastatic sites,” Nature Reviews Cancer, vol. 2, no. 8, pp. 563–572, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. A. E. Karnoub, A. B. Dash, A. P. Vo et al., “Mesenchymal stem cells within tumour stroma promote breast cancer metastasis,” Nature, vol. 449, no. 7162, pp. 557–563, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. W. Zhu, W. Xu, R. Jiang et al., “Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo,” Experimental and Molecular Pathology, vol. 80, no. 3, pp. 267–274, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. G. Lorusso and C. Rüegg, “The tumor microenvironment and its contribution to tumor evolution toward metastasis,” Histochemistry and Cell Biology, vol. 130, no. 6, pp. 1091–1103, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Colak, C. D. Zimberlin, and E. Fessler, “Decreased mitochondrial priming determines chemoresistance of colon cancer stem cells,” Cell Death & Differentiation, vol. 21, no. 7, pp. 1170–1177, 2014. View at Publisher · View at Google Scholar
  56. G. Bertolini, L. Roz, P. Perego et al., “Highly tumorigenic lung cancer CD133+ cells display stem-like features and are spared by cisplatin treatment,” Proceedings of the National Acadamy of Sciences of the United States of America, vol. 106, no. 38, pp. 16281–16286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Ma, T. K. Lee, B.-J. Zheng, K. W. Chan, and X.-Y. Guan, “CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway,” Oncogene, vol. 27, no. 12, pp. 1749–1758, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Todaro, M. P. Alea, A. B. di Stefano et al., “Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4,” Cell Stem Cell, vol. 1, no. 4, pp. 389–402, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Eramo, L. Ricci-Vitiani, A. Zeuner et al., “Chemotherapy resistance of glioblastoma stem cells,” Cell Death & Differentiation, vol. 13, no. 7, pp. 1238–1241, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. C. Ginestier, S. Liu, M. E. Diebel et al., “CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts,” The Journal of Clinical Investigation, vol. 120, no. 2, pp. 485–497, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Scheel, T. Onder, A. Karnoub, R. A. Weinberg, and J. E. Talmadge, “Adaptation versus selection: the origins of metastatic behavior,” Cancer Research, vol. 67, no. 24, pp. 11476–11480, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. I. Almendros and D. Gozal, “Intermittent hypoxia and cancer: undesirable bed partners?” Respiratory Physiology & Neurobiology, vol. 256, pp. 79–86, 2018. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Vaupel and A. Mayer, “Hypoxia in cancer: significance and impact on clinical outcome,” Cancer and Metastasis Reviews, vol. 26, no. 2, pp. 225–239, 2007. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Song and G. Li, “CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell homing and engraftment to tumors,” Cytotherapy, vol. 13, no. 5, pp. 549–561, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. W. Lin, L. Xu, S. Zwingenberger, E. Gibon, S. B. Goodman, and G. Li, “Mesenchymal stem cells homing to improve bone healing,” Journal of Orthopaedic Translation, vol. 9, pp. 19–27, 2017. View at Publisher · View at Google Scholar · View at Scopus
  66. E. Spaeth, A. Klopp, J. Dembinski, M. Andreeff, and F. Marini, “Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells,” Gene Therapy, vol. 15, no. 10, pp. 730–738, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Lee, S. El Andaloussi, and M. J. A. Wood, “Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy,” Human Molecular Genetics, vol. 21, no. 1, Article ID dds317, pp. R125–R134, 2012. View at Publisher · View at Google Scholar · View at Scopus
  68. A. M. M. T. Reza, Y.-J. Choi, H. Yasuda, and J.-H. Kim, “Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells,” Scientific Reports, vol. 6, 2016. View at Google Scholar · View at Scopus
  69. M. Ono, N. Kosaka, N. Tominaga et al., “Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells,” Science Signaling, vol. 7, no. 332, 2014. View at Publisher · View at Google Scholar
  70. S. Kim, H.-J. Sohn, H.-J. Lee et al., “Use of engineered exosomes expressing HLA and costimulatory molecules to generate antigen-specific CD8(+) T cells for adoptive cell therapy,” Journal of Immunotherapy, vol. 40, no. 3, pp. 83–93, 2017. View at Publisher · View at Google Scholar · View at Scopus
  71. D. S. Chulpanova, K. V. Kitaeva, L. G. Tazetdinova, V. James, A. A. Rizvanov, and V. V. Solovyeva, “Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment,” Frontiers in Pharmacology, vol. 9, p. 259, 2018. View at Publisher · View at Google Scholar
  72. J. Zhang, L. Hou, X. Wu et al., “Inhibitory effect of genetically engineered mesenchymal stem cells with Apoptin on hepatoma cells in vitro and in vivo,” Molecular and Cellular Biochemistry, vol. 416, no. 1-2, pp. 193–203, 2016. View at Publisher · View at Google Scholar · View at Scopus
  73. A. Pessina, V. Coccè, L. Pascucci et al., “Mesenchymal stromal cells primed with Paclitaxel attract and kill leukaemia cells, inhibit angiogenesis and improve survival of leukaemia-bearing mice,” British Journal of Haematology, vol. 160, no. 6, pp. 766–778, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Duchi, G. Sotgiu, E. Lucarelli et al., “Mesenchymal stem cells as delivery vehicle of porphyrin loaded nanoparticles: effective photoinduced in vitro killing of osteosarcoma,” Journal of Controlled Release, vol. 168, no. 2, pp. 225–237, 2013. View at Publisher · View at Google Scholar · View at Scopus
  75. A. Bonomi, N. Steimberg, A. Benetti et al., “Paclitaxel-releasing mesenchymal stromal cells inhibit the growth of multiple myeloma cells in a dynamic 3D culture system,” Hematological Oncology, vol. 35, no. 4, pp. 693–702, 2017. View at Publisher · View at Google Scholar · View at Scopus
  76. A. T. Brini, V. Coccè, L. M. J. Ferreira et al., “Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel,” Expert Opinion on Drug Delivery, vol. 13, no. 6, pp. 789–798, 2016. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Nakamizo, F. Marini, T. Amano et al., “Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas,” Cancer Research, vol. 65, no. 8, pp. 3307–3318, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. C. Ren, S. Kumar, D. Chanda et al., “Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model,” Gene Therapy, vol. 15, no. 21, pp. 1446–1453, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. X. Li, Y. Lu, W. Huang et al., “In vitro effect of adenovirus-mediated human Gamma Interferon gene transfer into human mesenchymal stem cells for chronic myelogenous leukemia,” Hematological Oncology, vol. 24, no. 3, pp. 151–158, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. M. R. Loebinger, A. Eddaoudi, D. Davies, and S. M. Janes, “Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer,” Cancer Research, vol. 69, no. 10, pp. 4134–4142, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. S. M. Kim, J. H. Oh, S. A. Park et al., “Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy,” Stem Cells, vol. 28, no. 12, pp. 2217–2228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. R. Uchibori, T. Okada, T. Ito et al., “Retroviral vector-producing mesenchymal stem cells for targeted suicide cancer gene therapy,” The Journal of Gene Medicine, vol. 11, no. 5, pp. 373–381, 2009. View at Publisher · View at Google Scholar · View at Scopus
  83. W. Y. Lee, T. Zhang, C. P. Lau, C. C. Wang, K. M. Chan, and G. Li, “Immortalized human fetal bone marrow-derived mesenchymal stromal cell expressing suicide gene for anti-tumor therapy in vitro and in vivo,” Cytotherapy, vol. 15, no. 12, pp. 1484–1497, 2013. View at Publisher · View at Google Scholar
  84. C. Song, J. Xiang, J. Tang et al., “Thymidine kinase gene modified bone marrow mesenchymal stem cells as vehicles for antitumor therapy,” Human Gene Therapy, vol. 22, no. 4, pp. 439–449, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. B. Yan, Q. Chen, K. Shimada et al., “Histone deacetylase inhibitor targets CD123/CD47-positive cells and reverse chemoresistance phenotype in acute myeloid leukemia,” Leukemia, 2018. View at Google Scholar · View at Scopus
  86. H. Okada and I. F. Pollack, “Cytokine gene therapy for malignant glioma,” Expert Opinion on Biological Therapy, vol. 4, no. 10, pp. 1609–1620, 2004. View at Publisher · View at Google Scholar · View at Scopus
  87. X. Xu, G. Yang, H. Zhang, and G. D. Prestwich, “Evaluating dual activity LPA receptor pan-antagonist/autotaxin inhibitors as anti-cancer agents in vivo using engineered human tumors,” Prostaglandins & Other Lipid Mediators, vol. 89, no. 3-4, pp. 140–146, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. X. Chen, X. Lin, J. Zhao et al., “A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs,” Molecular Therapy, vol. 16, no. 4, pp. 749–756, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Xin, T. Kikuchi, S. Andarini et al., “Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells,” European Journal of Immunology, vol. 35, no. 5, pp. 1371–1380, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. H. Xin, M. Kanehira, H. Mizuguchi et al., “Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells,” Stem Cells, vol. 25, no. 7, pp. 1618–1626, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. H. Xin, R. Sun, M. Kanehira et al., “Intratracheal delivery of CX3CL1-expressing mesenchymal stem cells to multiple lung tumors,” Molecular Medicine, vol. 15, no. 9-10, pp. 321–327, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. J. Veevers-Lowe, S. G. Ball, A. Shuttleworth, and C. M. Kielty, “Mesenchymal stem cell migration is regulated by fibronectin through alpha 5 beta 1-integrin-mediated activation of PDGFR-beta and potentiation of growth factor signals,” Journal of Cell Science, vol. 124, no. 8, pp. 1288–1300, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. S. Camorani, B. S. Hill, R. Fontanella et al., “Inhibition of bone marrow-derived mesenchymal stem cells homing towards triple-negative breast cancer microenvironment using an Anti-PDGFR beta aptamer,” Theranostics, vol. 7, no. 14, pp. 3595–3607, 2017. View at Publisher · View at Google Scholar · View at Scopus
  94. A. M. Roccaro, A. Sacco, W. G. Purschke et al., “SDF-1 inhibition targets the bone marrow niche for cancer therapy,” Cell Reports, vol. 9, no. 1, pp. 118–128, 2014. View at Publisher · View at Google Scholar · View at Scopus
  95. S. P. Monga, “Beta-Catenin Signaling and Roles in Liver Homeostasis, Injury, and Tumorigenesis,” Gastroenterology, vol. 148, no. 7, pp. 1294–1310, 2015. View at Publisher · View at Google Scholar · View at Scopus
  96. M. A. Chiurillo, “Role of the Wnt/beta-catenin pathway in gastric cancer: an in-depth literature review,” World Journal of Experimental Medicine, vol. 5, no. 2, pp. 84–102, 2015. View at Publisher · View at Google Scholar
  97. T. D. King, M. J. Suto, and Y. Li, “The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer,” Journal of Cellular Biochemistry, vol. 113, no. 1, pp. 13–18, 2012. View at Publisher · View at Google Scholar
  98. V. R. Dasari, K. Kaur, K. K. Velpula et al., “Upregulation of PTEN in glioma cells by cord blood mesenchymal stem cells inhibits migration via downregulation of the PI3K/Akt pathway,” PLoS ONE, vol. 5, no. 4, Article ID e10350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. N. Wu, Y. Zhang, H. Wang et al., “Overexpression of hepatocyte nuclear factor 4alpha in human mesenchymal stem cells suppresses hepatocellular carcinoma development through Wnt/beta-catenin signaling pathway downregulation,” Cancer Biology & Therapy, vol. 17, no. 5, pp. 558–565, 2016. View at Publisher · View at Google Scholar
  100. H. Niess, J. C. von Einem, M. N. Thomas et al., “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, vol. 15, no. 1, p. 237, 2015. View at Publisher · View at Google Scholar
  101. M. T. Schweizer, H. Wang, T. J. Bivalacqua et al., “A phase I study to assess the safety and cancer-homing ability of allogeneic bone marrow-derived mesenchymal stem cells in men with localized prostate cancer,” Stem Cells Translational Medicine, vol. 8, no. 5, pp. 441–449, 2019. View at Publisher · View at Google Scholar