Role of Mesenchymal Stem Cells in Cancer Development and Their Use in Cancer Therapy

  • Nedime SerakinciEmail author
  • Pinar Tulay
  • Rasime Kalkan
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1083)


Stem cells have the ability to perpetuate themselves through self-renewal and generate mature cells of a particular tissue through differentiation. Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis – supporting tissue regeneration. MSCs are rare pluripotent cells supporting hematopoietic and mesenchymal cell lineages. MSCs have a great therapeutic potential in cancer therapy, as well as stem cell exosome and/or microvesicle-mediated tissue regeneration. In this review, the use of hMSCs in stem cell-mediated cancer therapy is discussed.


Cancer development Cancer therapy Mesenchymal stem cells Stem cell-mediated cancer therapy 



Bone marrow-mesenchymal stem cells


Germ line stem cells


Hepatocyte growth factor


Indoleamine 2,3-dioxygenase




Major histocompatibility complex


Mesenchymal stem cells


Rheumatoid arthritis


  1. Abdul-Ghani, R., Ohana, P., Matouk, I., Ayesh, S., Ayesh, B., Laster, M., Bibi, O., Giladi, H., Molnar-Kimber, K., Sughayer, M. A., De Groot, N., & Hochberg, A. (2000). Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells. Molecular Therapy, 2, 539–544.Google Scholar
  2. Aboody, K. S., Najbauer, J., & Danks, M. K. (2008). Stem and progenitor cell-mediated tumor selective gene therapy. Gene Therapy, 15, 739–752.Google Scholar
  3. Barcellos-De-Souza, P., Gori, V., Bambi, F., & Chiarugi, P. (2013). Tumor microenvironment: Bone marrow-mesenchymal stem cells as key players. Biochimica et Biophysica Acta, 1836, 321–335.Google Scholar
  4. Barkholt, L., Flory, E., Jekerle, V., Lucas-Samuel, S., Ahnert, P., Bisset, L., Buscher, D., Fibbe, W., Foussat, A., Kwa, M., Lantz, O., Maciulaitis, R., Palomaki, T., Schneider, C. K., Sensebe, L., Tachdjian, G., Tarte, K., Tosca, L., & Salmikangas, P. (2013). Risk of tumorigenicity in mesenchymal stromal cell-based therapies–bridging scientific observations and regulatory viewpoints. Cytotherapy, 15, 753–759.Google Scholar
  5. Barrilleaux, B. L., Fischer-Valuck, B. W., Gilliam, J. K., Phinney, D. G., & O’connor, K. C. (2010). Activation of CD74 inhibits migration of human mesenchymal stem cells. In Vitro Cellular & Developmental Biology Animal, 46, 566–572.Google Scholar
  6. Batsali, A. K., Kastrinaki, M. C., Papadaki, H. A., & Pontikoglou, C. (2013). Mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord: Biological properties and emerging clinical applications. Current Stem Cell Research & Therapy, 8, 144–155.Google Scholar
  7. Bentzon, J. F., Stenderup, K., Hansen, F. D., Schroder, H. D., Abdallah, B. M., Jensen, T. G., & Kassem, M. (2005). Tissue distribution and engraftment of human mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene. Biochemical and Biophysical Research Communications, 330, 633–640.Google Scholar
  8. Bernardo, M. E., Emons, J. A., Karperien, M., Nauta, A. J., Willemze, R., Roelofs, H., Romeo, S., Marchini, A., Rappold, G. A., Vukicevic, S., Locatelli, F., & Fibbe, W. E. (2007). Human mesenchymal stem cells derived from bone marrow display a better chondrogenic differentiation compared with other sources. Connective Tissue Research, 48, 132–140.Google Scholar
  9. Bexell, D., Gunnarsson, S., Tormin, A., Darabi, A., Gisselsson, D., Roybon, L., Scheding, S., & Bengzon, J. (2009). Bone marrow multipotent mesenchymal stroma cells act as pericyte-like migratory vehicles in experimental gliomas. Molecular Therapy, 17, 183–190.Google Scholar
  10. Bhang, S. H., Lee, S., Shin, J. Y., Lee, T. J. & B.S., K. (2012) Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization. Tissue Engineering. Part A, 18, 2138–2147.PubMedCentralPubMedGoogle Scholar
  11. Bian, Z. Y., Fan, Q. M., Li, G., Xu, W. T., & Tang, T. T. (2010). Human mesenchymal stem cells promote growth of osteosarcoma: Involvement of interleukin-6 in the interaction between human mesenchymal stem cells and Saos-2. Cancer Science, 101, 2554–2560.Google Scholar
  12. Bilsland, A. E., Fletcher-Monaghan, A., & Keith, W. N. (2005). Properties of a telomerase specific Cre/Lox switch for transcriptionally targeted cancer gene therapy. Neoplasia, 7, 1020–1029.PubMedCentralPubMedGoogle Scholar
  13. Bischoff, D. S., Makhijani, N. S., & Yamaguchi, D. T. (2012). Constitutive expression of human telomerase enhances the proliferation potential of human mesenchymal stem cells. BioResearch Open Access, 1, 273–279.PubMedCentralPubMedGoogle Scholar
  14. Boiret, N., Rapatel, C., Veyrat-Masson, R., Guillouard, L., Guerin, J. J., Pigeon, P., Descamps, S., Boisgard, S., & Berger, M. G. (2005). Characterization of nonexpanded mesenchymal progenitor cells from normal adult human bone marrow. Experimental Hematology, 33, 219–225.Google Scholar
  15. Brooke, G., Cook, M., Blair, C., Han, R., Heazlewood, C., Jones, B., Kambouris, M., Kollar, K., Mctaggart, S., Pelekanos, R., Rice, A., Rossetti, T., & Atkinson, K. (2007). Therapeutic applications of mesenchymal stromal cells. Seminars in Cell & Developmental Biology, 18, 846–858.Google Scholar
  16. Bulman, S. E., Barron, V., Coleman, C. M., & Barry, F. (2013). Enhancing the mesenchymal stem cell therapeutic response: Cell localization and support for cartilage repair. Tissue Engineering. Part B, Reviews, 19, 58–68.Google Scholar
  17. Burdon, T., Smith, A., & Savatier, P. (2002). Signalling, cell cycle and pluripotency in embryonic stem cells. Trends in Cell Biology, 12, 432–438.Google Scholar
  18. Burns, J. S., Abdallah, B. M., Guldberg, P., Rygaard, J., Schroder, H. D., & Kassem, M. (2005). Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Research, 65, 3126–3135.Google Scholar
  19. Calio, M. L., Marinho, D. S., Ko, G. M., Ribeiro, R. R., Carbonel, A. F., Oyama, L. M., Ormanji, M., Guirao, T. P., Calio, P. L., Reis, L. A., Simoes Mde, J., Lisboa-Nascimento, T., Ferreira, A. T., & Bertoncini, C. R. (2014). Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model. Free Radical Biology & Medicine, 70, 141–154.Google Scholar
  20. Campagnoli, C., Roberts, I. A., Kumar, S., Bennett, P. R., Bellantuono, I., & Fisk, N. M. (2001). Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 98, 2396–2402.Google Scholar
  21. Carvalho, J. L., Braga, V. B., Melo, M. B., Campos, A. C., Oliveira, M. S., Gomes, D. A., Ferreira, A. J., Santos, R. A., & Goes, A. M. (2013). Priming mesenchymal stem cells boosts stem cell therapy to treat myocardial infarction. Journal of Cellular and Molecular Medicine, 17, 617–625.PubMedCentralPubMedGoogle Scholar
  22. Chamberlain, G., Fox, J., Ashton, B., & Middleton, J. (2007). Concise review: Mesenchymal stem cells: Their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells, 25, 2739–2749.Google Scholar
  23. Chang, Y. J., Shih, D. T., Tseng, C. P., Hsieh, T. B., Lee, D. C., & Hwang, S. M. (2006). Disparate mesenchyme-lineage tendencies in mesenchymal stem cells from human bone marrow and umbilical cord blood. Stem Cells, 24, 679–685.Google Scholar
  24. Chen, Y., Shao, J. Z., Xiang, L. X., Dong, X. J., & Zhang, G. R. (2008). Mesenchymal stem cells: A promising candidate in regenerative medicine. The International Journal of Biochemistry & Cell Biology, 40, 815–820.Google Scholar
  25. Christensen, R., Alsner, J., Brandt Sorensen, F., Dagnaes-Hansen, F., Kolvraa, S., & Serakinci, N. (2008) Transformation of human mesenchymal stem cells in radiation carcinogenesis: Long-term effect of ionizing radiation. Regenerative Medicine, 3, 849–861.Google Scholar
  26. Cipriani, P., Di Benedetto, P., Liakouli, V., Del Papa, B., Di Padova, M., Di Ianni, M., Marrelli, A., Alesse, E., & Giacomelli, R. (2013). Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: Implications for cellular-based therapy. Clinical and Experimental Immunology, 173, 195–206.PubMedCentralPubMedGoogle Scholar
  27. Coffelt, S. B., Marini, F. C., Watson, K., Zwezdaryk, K. J., Dembinski, J. L., Lamarca, H. L., Tomchuck, S. L., Honer Zu Bentrup, K., Danka, E. S., Henkle, S. L., & Scandurro, A. B. (2009). The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proceedings of the National Academy of Sciences of the United States of America, 106, 3806–3811.PubMedCentralPubMedGoogle Scholar
  28. Correa, P., & Houghton, J. (2007). Carcinogenesis of helicobacter pylori. Gastroenterology, 133, 659–672.Google Scholar
  29. Counter, C. M., Avilion, A. A., Lefeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992). Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. The EMBO Journal, 11, 1921–1929.PubMedCentralPubMedGoogle Scholar
  30. Das, B., Tsuchida, R., Malkin, D., Koren, G., Baruchel, S., & Yeger, H. (2008). Hypoxia enhances tumor stemness by increasing the invasive and tumorigenic side population fraction. Stem Cells, 26, 1818–1830.PubMedGoogle Scholar
  31. De Bari, C., Dell’accio, F., Tylzanowski, P., & Luyten, F. P. (2001). Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis and Rheumatism, 44, 1928–1942.PubMedGoogle Scholar
  32. De Boeck, A., Pauwels, P., Hensen, K., Rummens, J. L., Westbroek, W., Hendrix, A., Maynard, D., Denys, H., Lambein, K., Braems, G., Gespach, C., Bracke, M., & De Wever, O. (2013). Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression through paracrine neuregulin 1/HER3 signalling. Gut, 62, 550–560.PubMedGoogle Scholar
  33. Dennis, J. E., Cohen, N., Goldberg, V. M., & Caplan, A. I. (2004). Targeted delivery of progenitor cells for cartilage repair. Journal of Orthopaedic Research, 22, 735–741.PubMedGoogle Scholar
  34. Di Bella, C., Farlie, P., & Penington, A. J. (2008). Bone regeneration in a rabbit critical-sized skull defect using autologous adipose-derived cells. Tissue Engineering. Part A, 14, 483–490.PubMedGoogle Scholar
  35. Di Rocco, G., Tritarelli, A., Toietta, G., Gatto, I., Iachininoto, M. G., Pagani, F., Mangoni, A., Straino, S., & Capogrossi, M. C. (2008). Spontaneous myogenic differentiation of Flk-1-positive cells from adult pancreas and other nonmuscle tissues. American Journal of Physiology. Cell Physiology, 294, C604–C612.PubMedGoogle Scholar
  36. Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Noel, D., & Jorgensen, C. (2003). Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood, 102, 3837–3844.PubMedGoogle Scholar
  37. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D., & Horwitz, E. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy, 8, 315–317.Google Scholar
  38. D’souza, N., Burns, J. S., Grisendi, G., Candini, O., Veronesi, E., Piccinno, S., Horwitz, E. M., Paolucci, P., Conte, P., & Dominici, M. (2012). MSC and tumors: Homing, differentiation, and secretion influence therapeutic potential. Advances in Biochemical Engineering/Biotechnology, 130, 209–266.Google Scholar
  39. Erices, A., Conget, P., & Minguell, J. J. (2000). Mesenchymal progenitor cells in human umbilical cord blood. British Journal of Haematology, 109, 235–242.Google Scholar
  40. Forbes, G. M., Sturm, M. J., Leong, R. W., Sparrow, M. P., Segarajasingam, D., Cummins, A. G., Phillips, M., & Herrmann, R. P. (2014). A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy. Clinical Gastroenterology and Hepatology, 12, 64–71.Google Scholar
  41. Friedenstein, A. Y. (1968). Induction of bone tissue by transitional epithelium. Clinical Orthopaedics and Related Research, 59, 21–37.PubMedGoogle Scholar
  42. Friedenstein, A. J., Chailakhjan, R. K., & Lalykina, K. S. (1970). The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell and Tissue Kinetics, 3, 393–403.Google Scholar
  43. Fukuchi, Y., Nakajima, H., Sugiyama, D., Hirose, I., Kitamura, T., & Tsuji, K. (2004). Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells, 22, 649–658.Google Scholar
  44. Furlani, D., Li, W., Pittermann, E., Klopsch, C., Wang, L., Knopp, A., Jungebluth, P., Thedinga, E., Havenstein, C., Westien, I., Ugurlucan, M., Li, R. K., Ma, N., & Steinhoff, G. (2009). A transformed cell population derived from cultured mesenchymal stem cells has no functional effect after transplantation into the injured heart. Cell Transplantation, 18, 319–331.Google Scholar
  45. Gao, Z., Zhang, L., Hu, J., & Sun, Y. (2013). Mesenchymal stem cells: A potential targeted-delivery vehicle for anti-cancer drug, loaded nanoparticles. Nanomedicine, 9, 174–184.PubMedGoogle Scholar
  46. Goodwin, H. S., Bicknese, A. R., Chien, S. N., Bogucki, B. D., Quinn, C. O., & Wall, D. A. (2001). Multilineage differentiation activity by cells isolated from umbilical cord blood: Expression of bone, fat, and neural markers. Biology of Blood and Marrow Transplantation, 7, 581–588.PubMedGoogle Scholar
  47. Hahn, W. C., & Weinberg, R. A. (2002). Modelling the molecular circuitry of cancer. Nature Reviews Cancer, 2, 331–341.PubMedGoogle Scholar
  48. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144, 646–674.PubMedGoogle Scholar
  49. Hanna, J., Cheng, A. W., Saha, K., Kim, J., Lengner, C. J., Soldner, F., Cassady, J. P., Muffat, J., Carey, B. W., & Jaenisch, R. (2010). Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs. Proceedings of the National Academy of Sciences of the United States of America, 107, 9222–9227.PubMedCentralPubMedGoogle Scholar
  50. Harbo, M., Koelvraa, S., Serakinci, N., & Bendix, L. (2012). Telomere dynamics in human mesenchymal stem cells after exposure to acute oxidative stress. DNA Repair (Amst), 11, 774–779.Google Scholar
  51. Honoki, K., Fujii, H., & Tsujiuchi, T. (2011) Cancer stem cell niche: The role of Mesenchymal stem cells in tumor microenvironment.Google Scholar
  52. Hoogduijn, M. J., Popp, F., Verbeek, R., Masoodi, M., Nicolaou, A., Baan, C., & Dahlke, M. H. (2010). The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. International Immunopharmacology, 10, 1496–1500.Google Scholar
  53. Ito, M., Hiramatsu, H., Kobayashi, K., Suzue, K., Kawahata, M., Hioki, K., Ueyama, Y., Koyanagi, Y., Sugamura, K., Tsuji, K., Heike, T., & Nakahata, T. (2002). NOD/SCID/gamma(c)(null) mouse: An excellent recipient mouse model for engraftment of human cells. Blood, 100, 3175–3182.Google Scholar
  54. Ji, K. H., Xiong, J., Fan, L. X., Hu, K. M., & Liu, H. Q. (2009). Multilineage differentiation capability comparison between Mesenchymal stem cells and Multipotent adult progenitor cells. Advanced Studies in Biology, 1, 25–35.Google Scholar
  55. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W. C., Largaespada, D. A., & Verfaillie, C. M. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418, 41–49.PubMedCentralPubMedGoogle Scholar
  56. Jung, Y., Kim, J. K., Shiozawa, Y., Wang, J., Mishra, A., Joseph, J., Berry, J. E., Mcgee, S., Lee, E., Sun, H., Jin, T., Zhang, H., Dai, J., Krebsbach, P. H., Keller, E. T., Pienta, K. J., & Taichman, R. S. (2013). Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis. Nature Communications, 4, 1795.PubMedCentralPubMedGoogle Scholar
  57. Karnoub, A. E., Dash, A. B., Vo, A. P., Sullivan, A., Brooks, M. W., Bell, G. W., Richardson, A. L., Polyak, K., Tubo, R., & Weinberg, R. A. (2007). Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 449, 557–563.Google Scholar
  58. Kern, S., Eichler, H., Stoeve, J., Kluter, H., & Bieback, K. (2006). Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 24, 1294–1301.Google Scholar
  59. Kidd, S., Spaeth, E., Dembinski, J. L., Dietrich, M., Watson, K., Klopp, A., Battula, V. L., Weil, M., Andreeff, M., & Marini, F. C. (2009). Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells, 27, 2614–2623.PubMedCentralPubMedGoogle Scholar
  60. Kim, N., & Cho, S. G. (2013). Clinical applications of mesenchymal stem cells. The Korean Journal of Internal Medicine, 28, 387–402.PubMedCentralPubMedGoogle Scholar
  61. Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science, 266, 2011–2015.Google Scholar
  62. Kim, J. B., O’hare, M. J., & Stein, R. (2004). Models of breast cancer: Is merging human and animal models the future? Breast Cancer Research, 6, 22–30.Google Scholar
  63. Kim, J. W., Ha, K. Y., Molon, J. N., & Kim, Y. H. (2013a). Bone marrow-derived mesenchymal stem cell transplantation for chronic spinal cord injury in rats: Comparative study between intralesional and intravenous transplantation. Spine (Phila Pa 1976), 38, E1065–E1074.Google Scholar
  64. Kim, N., Im, K. I., Lim, J. Y., Jeon, E. J., Nam, Y. S., Kim, E. J., & Cho, S. G. (2013b). Mesenchymal stem cells for the treatment and prevention of graft-versus-host disease: Experiments and practice. Annals of Hematology, 92, 1295–1308.Google Scholar
  65. Kitamura, H., Okudela, K., Yazawa, T., Sato, H., & Shimoyamada, H. (2009). Cancer stem cell: Implications in cancer biology and therapy with special reference to lung cancer. Lung Cancer, 66, 275–281.Google Scholar
  66. Komata, T., Kondo, Y., Kanzawa, T., Hirohata, S., Koga, S., Sumiyoshi, H., Srinivasula, S. M., Barna, B. P., Germano, I. M., Takakura, M., Inoue, M., Alnemri, E. S., Shay, J. W., Kyo, S., & Kondo, S. (2001). Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Cancer Research, 61, 5796–5802.Google Scholar
  67. Korbling, M., Estrov, Z., & Champlin, R. (2003). Adult stem cells and tissue repair. Bone Marrow Transplantation, 32(Suppl 1), S23–S24.Google Scholar
  68. Kortesidis, A., Zannettino, A., Isenmann, S., Shi, S., Lapidot, T., & Gronthos, S. (2005). Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood, 105, 3793–3801.Google Scholar
  69. Lazennec, G., & Jorgensen, C. (2008). Concise review: Adult multipotent stromal cells and cancer: Risk or benefit? Stem Cells, 26, 1387–1394.PubMedCentralPubMedGoogle Scholar
  70. Li, L., & Xie, T. (2005). Stem cell niche: Structure and function. Annual Review of Cell and Developmental Biology, 21, 605–631.Google Scholar
  71. Li, H., Fu, X., Ouyang, Y., Cai, C., Wang, J., & Sun, T. (2006). Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell and Tissue Research, 326, 725–736.Google Scholar
  72. Lin, H. (2002). The stem-cell niche theory: Lessons from flies. Nature Reviews. Genetics, 3, 931–940.Google Scholar
  73. Liu, S., Ginestier, C., Ou, S. J., Clouthier, S. G., Patel, S. H., Monville, F., Korkaya, H., Heath, A., Dutcher, J., Kleer, C. G., Jung, Y., Dontu, G., Taichman, R., & Wicha, M. S. (2011). Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Research, 71, 614–624.PubMedCentralPubMedGoogle Scholar
  74. Loebinger, M. R., Kyrtatos, P. G., Turmaine, M., Price, A. N., Pankhurst, Q., Lythgoe, M. F., & Janes, S. M. (2009). Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Research, 69, 8862–8867.PubMedCentralPubMedGoogle Scholar
  75. Louis, S. A., Zapf, R., Clarke, E., Thomas, T. E., & Sutherland, H. J. (2001). A negative-selection strategy for depleting myeloma cells from patients’ BM and/or leukapheresis blood. Cytotherapy, 3, 489–504.Google Scholar
  76. Ma, T. (2010). Mesenchymal stem cells: From bench to bedside. World Journal of Stem Cells, 2, 13–17.PubMedCentralPubMedGoogle Scholar
  77. Madrigal, M., Rao, K. S., & Riordan, N. H. (2014). A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. Journal of Translational Medicine, 12, 260.PubMedCentralPubMedGoogle Scholar
  78. Marinova-Mutafchieva, L., Williams, R. O., Mauri, C., Mason, L. J., Walmsley, M. J., Taylor, P. C., Feldmann, M., & Maini, R. N. (2000). A comparative study into the mechanisms of action of anti-tumor necrosis factor alpha, anti-CD4, and combined anti-tumor necrosis factor alpha/anti-CD4 treatment in early collagen-induced arthritis. Arthritis and Rheumatism, 43, 638–644.Google Scholar
  79. Martinez, C., Hofmann, T. J., Marino, R., Dominici, M., & Horwitz, E. M. (2007). Human bone marrow mesenchymal stromal cells express the neural ganglioside GD2: A novel surface marker for the identification of MSCs. Blood, 109, 4245–4248.PubMedCentralPubMedGoogle Scholar
  80. Menon, L. G., Picinich, S., Koneru, R., Gao, H., Lin, S. Y., Koneru, M., Mayer-Kuckuk, P., Glod, J., & Banerjee, D. (2007). Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells, 25, 520–528.Google Scholar
  81. Menon, L. G., Kelly, K., Yang, H. W., Kim, S. K., Black, P. M., & Carroll, R. S. (2009). Human bone marrow-derived mesenchymal stromal cells expressing S-TRAIL as a cellular delivery vehicle for human glioma therapy. Stem Cells, 27, 2320–2330.Google Scholar
  82. Meza-Zepeda, L. A., Noer, A., Dahl, J. A., Micci, F., Myklebost, O., & Collas, P. (2008). High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence. Journal of Cellular and Molecular Medicine, 12, 553–563.Google Scholar
  83. Miura, M., Miura, Y., Padilla-Nash, H. M., Molinolo, A. A., Fu, B., Patel, V., Seo, B. M., Sonoyama, W., Zheng, J. J., Baker, C. C., Chen, W., Ried, T., & Shi, S. (2006). Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation. Stem Cells (Dayton, Ohio), 24(4), 1095–1103.Google Scholar
  84. Momin, E. N., Vela, G., Zaidi, H. A., & Quinones-Hinojosa, A. (2010). The oncogenic potential of mesenchymal stem cells in the treatment of cancer: Directions for future research. Current Immunology Reviews, 6, 137–148.PubMedCentralPubMedGoogle Scholar
  85. Morrison, S. J., & Spradling, A. C. (2008). Stem cells and niches: Mechanisms that promote stem cell maintenance throughout life. Cell, 132(4), 598–611.PubMedCentralPubMedGoogle Scholar
  86. Mueller, S. M., & Glowacki, J. (2001). Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges. Journal of Cellular Biochemistry, 82, 583–590.Google Scholar
  87. Nguyen, S. T., Pham, V. Q., Phan, N. K., & Pham, P. V. (2014). Mesenchymal stem cell-based cancer gene therapy: Application and unresolved problems. Annual Research & Review in Biology, 4, 1387–1396.Google Scholar
  88. Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., Mckay, R., Nadal-Ginard, B., Bodine, D. M., Leri, A., & Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.Google Scholar
  89. Patel, S. A., Meyer, J. R., Greco, S. J., Corcoran, K. E., Bryan, M., & Rameshwar, P. (2010). Mesenchymal stem cells protect breast cancer cells through regulatory T cells: Role of mesenchymal stem cell-derived TGF-beta. Journal of Immunology, 184, 5885–5894.Google Scholar
  90. Peault, B., Rudnicki, M., Torrente, Y., Cossu, G., Tremblay, J. P., Partridge, T., Gussoni, E., Kunkel, L. M., & Huard, J. (2007). Stem and progenitor cells in skeletal muscle development, maintenance, and therapy. Molecular Therapy, 15, 867–877.Google Scholar
  91. Pevsner-Fischer, M., Levin, S., & Zipori, D. (2011). The origins of mesenchymal stromal cell heterogeneity. Stem Cell Reviews, 7, 560–568.Google Scholar
  92. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284, 143–147.Google Scholar
  93. Placencio, V. R., Li, X., Sherrill, T. P., Fritz, G., & Bhowmick, N. A. (2010). Bone marrow derived mesenchymal stem cells incorporate into the prostate during regrowth. PloS One, 5, e12920.PubMedCentralPubMedGoogle Scholar
  94. Plumb, J. A., Bilsland, A., Kakani, R., Zhao, J., Glasspool, R. M., Knox, R. J., Evans, T. R., & Keith, W. N. (2001). Telomerase-specific suicide gene therapy vectors expressing bacterial nitroreductase sensitize human cancer cells to the pro-drug CB1954. Oncogene, 20, 7797–7803.Google Scholar
  95. Prindull, G., Ben-Ishay, Z., Ebell, W., Bergholz, M., Dirk, T., & Prindull, B. (1987). CFU-F circulating in cord blood. Blut, 54, 351–359.Google Scholar
  96. Quante, M., Tu, S. P., Tomita, H., Gonda, T., Wang, S. S., Takashi, S., Baik, G. H., Shibata, W., Diprete, B., Betz, K. S., Friedman, R., Varro, A., Tycko, B., & Wang, T. C. (2011). Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell, 19, 257–272.PubMedCentralPubMedGoogle Scholar
  97. Quirici, N., Soligo, D., Bossolasco, P., Servida, F., Lumini, C., & Deliliers, G. L. (2002). Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Experimental Hematology, 30, 783–791.Google Scholar
  98. Rangarajan, A., & Weinberg, R. A. (2003). Opinion: Comparative biology of mouse versus human cells: Modelling human cancer in mice. Nature Reviews Cancer, 3, 952–959.Google Scholar
  99. Resnick, I. B., Barkats, C., Shapira, M. Y., Stepensky, P., Bloom, A. I., Shimoni, A., Mankuta, D., Varda-Bloom, N., Rheingold, L., Yeshurun, M., Bielorai, B., Toren, A., Zuckerman, T., Nagler, A. & Or, R. (2013) Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC). American Journal of Blood Research, 3, 225–238.Google Scholar
  100. Reyes, M., Lund, T., Lenvik, T., Aguiar, D., Koodie, L., & Verfaillie, C. M. (2001). Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood, 98, 2615–2625.Google Scholar
  101. Rosen, J. M., & Jordan, C. T. (2009). The increasing complexity of the cancer stem cell paradigm. Science, 324, 1670–1673.PubMedCentralPubMedGoogle Scholar
  102. Rubinstein, P., Dobrila, L., Rosenfield, R. E., Adamson, J. W., Migliaccio, G., Migliaccio, A. R., Taylor, P. E., & Stevens, C. E. (1995). Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. Proceedings of the National Academy of Sciences of the United States of America, 92, 10119–10122.PubMedCentralPubMedGoogle Scholar
  103. Rubio, D., Garcia-Castro, J., Martin, M. C., De La Fuente, R., Cigudosa, J. C., Lloyd, A. C., & Bernad, A. (2005). Spontaneous human adult stem cell transformation. Cancer Research, 65, 3035–3039.Google Scholar
  104. Rubio, D., Garcia, S., Paz, M. F., De La Cueva, T., Lopez-Fernandez, L. A., Lloyd, A. C., Garcia-Castro, J., & Bernad, A. (2008). Molecular characterization of spontaneous 17 mesenchymal stem cell transformation. PloS One, 3, e1398.PubMedCentralPubMedGoogle Scholar
  105. Sarosi, G., Brown, G., Jaiswal, K., Feagins, L. A., Lee, E., Crook, T. W., Souza, R. F., Zou, Y. S., Shay, J. W., & Spechler, S. J. (2008). Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett’s esophagus. Diseases of the Esophagus, 21, 43–50.Google Scholar
  106. Sasportas, L. S., Kasmieh, R., Wakimoto, H., Hingtgen, S., Van De Water, J. A., Mohapatra, G., Figueiredo, J. L., Martuza, R. L., Weissleder, R., & Shah, K. (2009). Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proceedings of the National Academy of Sciences of the United States of America, 106, 4822–4827.PubMedCentralPubMedGoogle Scholar
  107. Seo, S. H., Kim, K. S., Park, S. H., Suh, Y. S., Kim, S. J., Jeun, S. S., & Sung, Y. C. (2011). The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Therapy, 18, 488–495.PubMedCentralPubMedGoogle Scholar
  108. Serakinci, N., Guldberg, P., Burns, J. S., Abdallah, B., Schrodder, H., Jensen, T., & Kassem, M. (2004). Adult human mesenchymal stem cell as a target for neoplastic transformation. Oncogene, 23, 5095–5098.Google Scholar
  109. Serakinci, N., Christensen, R., Graakjaer, J., Cairney, C. J., Keith, W. N., Alsner, J., Saretzki, G., & Kolvraa, S. (2007). Ectopically hTERT expressing adult human mesenchymal stem cells are less radiosensitive than their telomerase negative counterpart. Experimental Cell Research, 313, 1056–1067.Google Scholar
  110. Serakinci, N., Graakjaer, J., & Kolvraa, S. (2008). Telomere stability and telomerase in mesenchymal stem cells. Biochimie, 90, 33–40.Google Scholar
  111. Serakinci, N., Christensen, R., Fahrioglu, U., Sorensen, F. B., Dagnæs-Hansen, F., Hajek, M., Jensen, T. H., Kolvraa, S., & Keith, N. W. (2011). Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma. Cancer Biotherapy & Radiopharmaceuticals, 26, 767–773.Google Scholar
  112. Serakinci, N., Fahrioglu, U., & Christensen, R. (2014). Mesenchymal stem cells, cancer challenges and new directions. European Journal of Cancer, 50, 1522–1530.Google Scholar
  113. Shah, K. (2013). Encapsulated stem cells for cancer therapy. Biomatter, 3(1), e24278.PubMedCentralPubMedGoogle Scholar
  114. Sharma, A. K., Fuller, N. J., Sullivan, R. R., Fulton, N., Hota, P. V., Harrington, D. A., Villano, J., Hagerty, J. A., & Cheng, E. Y. (2009). Defined populations of bone marrow derived mesenchymal stem and endothelial progenitor cells for bladder regeneration. The Journal of Urology, 182, 1898–1905.Google Scholar
  115. Shay, J. W., Pereira-Smith, O. M., & Wright, W. E. (1991). A role for both RB and p53 in the regulation of human cellular senescence. Experimental Cell Research, 196, 33–39.Google Scholar
  116. Shi, S., & Gronthos, S. (2003). Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. Journal of Bone and Mineral Research, 18, 696–704.Google Scholar
  117. Shinagawa, K., Kitadai, Y., Tanaka, M., Sumida, T., Kodama, M., Higashi, Y., Tanaka, S., Yasui, W., & Chayama, K. (2010). Mesenchymal stem cells enhance growth and metastasis of colon cancer. International Journal of Cancer, 127, 2323–2333.Google Scholar
  118. Simmons, P. J., & Torok-Storb, B. (1991). Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood, 78, 55–62.Google Scholar
  119. Simonsen, J. L., Rosada, C., Serakinci, N., Justesen, J., Stenderup, K., Rattan, S. I., Jensen, T. G., & Kassem, M. (2002). Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells. Nature Biotechnology, 20, 592–596.Google Scholar
  120. Sohni, A., & Verfaillie, C. M. (2013). Mesenchymal stem cells migration homing and tracking. Stem Cells International, 2013, 130763.PubMedCentralPubMedGoogle Scholar
  121. Soltysova, A., Altanerova, V., & Altaner, C. (2005). Cancer stem cells. Neoplasma, 52, 435–440.Google Scholar
  122. Sordi, V., Malosio, M. L., Marchesi, F., Mercalli, A., Melzi, R., Giordano, T., Belmonte, N., Ferrari, G., Leone, B. E., Bertuzzi, F., Zerbini, G., Allavena, P., Bonifacio, E., & Piemonti, L. (2005). Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood, 106, 419–427.Google Scholar
  123. Spaeth, E. L., Dembinski, J. L., Sasser, A. K., Watson, K., Klopp, A., Hall, B., Andreeff, M., & Marini, F. (2009). Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PloS One, 4, e4992.PubMedCentralPubMedGoogle Scholar
  124. Studeny, M., Marini, F. C., Champlin, R. E., Zompetta, C., Fidler, I. J., & Andreeff, M. (2002). Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Research, 62, 3603–3608.Google Scholar
  125. Studeny, M., Marini, F. C., Dembinski, J. L., Zompetta, C., Cabreira-Hansen, M., Bekele, B. N., Champlin, R. E., & Andreeff, M. (2004). Mesenchymal stem cells: Potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. Journal of the National Cancer Institute, 96, 1593–1603.Google Scholar
  126. Sun, X. Y., Nong, J., Qin, K., Warnock, G. L., & Dai, L. J. (2011). Mesenchymal stem cell-mediated cancer therapy: A dual-targeted strategy of personalized medicine. World Journal of Stem Cells, 3, 96–103.PubMedCentralPubMedGoogle Scholar
  127. Suzuki, K., Sun, R., Origuchi, M., Kanehira, M., Takahata, T., Itoh, J., Umezawa, A., Kijima, H., Fukuda, S., & Saijo, Y. (2011). Mesenchymal stromal cells promote tumor growth through the enhancement of neovascularization. Molecular Medicine, 17, 579–587.PubMedCentralPubMedGoogle Scholar
  128. Terskikh, A. V., Bryant, P. J., & Schwartz, P. H. (2006). Mammalian stem cells. Pediatric Research, 59, 13R–20R.Google Scholar
  129. Teven, C. M., Liu, X., Hu, N., Tang, N., Kim, S. H., Huang, E., Yang, K., Li, M., Gao, J. L., Liu, H., Natale, R. B., Luther, G., Luo, Q., Wang, L., Rames, R., Bi, Y., Luo, J., Luu, H. H., Haydon, R. C., Reid, R. R., & He, T. C. (2011). Epigenetic regulation of mesenchymal stem cells: A focus on osteogenic and adipogenic differentiation. Stem Cells International, 2011, 201371.PubMedCentralPubMedGoogle Scholar
  130. Tolar, J., Nauta, A. J., Osborn, M. J., Panoskaltsis Mortari, A., Mcelmurry, R. T., Bell, S., Xia, L., Zhou, N., Riddle, M., Schroeder, T. M., Westendorf, J. J., Mcivor, R. S., Hogendoorn, P. C., Szuhai, K., Oseth, L., Hirsch, B., Yant, S. R., Kay, M. A., Peister, A., Prockop, D. J., Fibbe, W. E., & Blazar, B. R. (2007). Sarcoma derived from cultured mesenchymal stem cells. Stem Cells, 25, 371–379.Google Scholar
  131. Tsai, M. S., Lee, J. L., Chang, Y. J., & Hwang, S. M. (2004). Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Human Reproduction, 19, 1450–1456.Google Scholar
  132. Tsai, K. S., Yang, S. H., Lei, Y. P., Tsai, C. C., Chen, H. W., Hsu, C. Y., Chen, L. L., Wang, H. W., Miller, S. A., Chiou, S. H., Hung, M. C., & Hung, S. C. (2011). Mesenchymal stem cells promote formation of colorectal tumors in mice. Gastroenterology, 141, 1046–1056.Google Scholar
  133. Van’t Hof, W., Mal, N., Huang, Y., Zhang, M., Popovic, Z., Forudi, F., Deans, R., & Penn, M. S. (2007). Direct delivery of syngeneic and allogeneic large-scale expanded multipotent adult progenitor cells improves cardiac function after myocardial infarct. Cytotherapy, 9, 477–487.Google Scholar
  134. Vellasamy, S., Sandrasaigaran, P., Vidyadaran, S., George, E., & Ramasamy, R. (2012). Isolation and characterisation of mesenchymal stem cells derived from human placenta tissue. World Journal of Stem Cells, 4, 53–61.PubMedCentralPubMedGoogle Scholar
  135. Villaron, E. M., Almeida, J., Lopez-Holgado, N., Alcoceba, M., Sanchez-Abarca, L. I., Sanchez-Guijo, F. M., Alberca, M., Perez-Simon, J. A., San Miguel, J. F., & Del Canizo, M. C. (2004). Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematologica, 89, 1421–1427.Google Scholar
  136. Wang, Y., Huso, D. L., Harrington, J., Kellner, J., Jeong, D. K., Turney, J., & Mcniece, I. K. (2005). Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy, 7, 509–519.Google Scholar
  137. Wynn, R. F., Hart, C. A., Corradi-Perini, C., O’neill, L., Evans, C. A., Wraith, J. E., Fairbairn, L. J., & Bellantuono, I. (2004). A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood, 104, 2643–2645.Google Scholar
  138. Wyrsch, A., Dalle Carbonare, V., Jansen, W., Chklovskaia, E., Nissen, C., Surbek, D., Holzgreve, W., Tichelli, A., & Wodnar-Filipowicz, A. (1999). Umbilical cord blood from preterm human fetuses is rich in committed and primitive hematopoietic progenitors with high proliferative and self-renewal capacity. Experimental Hematology, 27, 1338–1345.Google Scholar
  139. Yagi, H., & Kitagawa, Y. (2013). The role of mesenchymal stem cells in cancer development. Frontiers in Genetics, 4, 261.PubMedCentralPubMedGoogle Scholar
  140. Yang, C., Lei, D., Ouyang, W., Ren, J., Li, H., Hu, J., & Huang, S. (2014). Conditioned media from human adipose tissue-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells efficiently induced the apoptosis and differentiation in human glioma cell lines in vitro. BioMed Research International, 2014, 109389.Google Scholar
  141. Ye, H., Cheng, J., Tang, Y., Liu, Z., Xu, C., Liu, Y., & Sun, Y. (2012). Human bone marrow-derived mesenchymal stem cells produced TGFbeta contributes to progression and metastasis of prostate cancer. Cancer Investigation, 30, 513–518.Google Scholar
  142. Yu, B., Zhang, X., & Li, X. (2014). Exosomes derived from mesenchymal stem cells. International Journal of Molecular Sciences, 15, 4142–4157.PubMedCentralPubMedGoogle Scholar
  143. Zeng, H. L., Zhong, Q., Qin, Y. L., Bu, Q. Q., Han, X. A., Jia, H. T., & Liu, H. W. (2011). Hypoxia-mimetic agents inhibit proliferation and alter the morphology of human umbilical cord-derived mesenchymal stem cells. BMC Cell Biology, 12, 32.PubMedCentralPubMedGoogle Scholar
  144. Zhou, Y. F., Bosch-Marce, M., Okuyama, H., Krishnamachary, B., Kimura, H., Zhang, L., Huso, D. L., & Semenza, G. L. (2006). Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Research, 66, 10849–10854.Google Scholar
  145. Zhu, W., Xu, W., Jiang, R., Qian, H., Chen, M., Hu, J., Cao, W., Han, C., & Chen, Y. (2006). Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Experimental and Molecular Pathology, 80, 267–274.Google Scholar
  146. Zischek, C., Niess, H., Ischenko, I., Conrad, C., Huss, R., Jauch, K. W., Nelson, P. J., & Bruns, C. (2009). Targeting tumor stroma using engineered mesenchymal stem cells reduces the growth of pancreatic carcinoma. Annals of Surgery, 250, 747–753.Google Scholar
  147. Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I., Mizuno, H., Alfonso, Z. C., Fraser, J. K., Benhaim, P., & Hedrick, M. H. (2002). Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, 13, 4279–4295.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of Medical GeneticsNear East UniversityNicosiaCyprus
  2. 2.Faculty of Arts and Sciences, Department of Molecular Biology and GeneticsNear East UniversityNicosiaCyprus

Personalised recommendations