Mesenchymal Stem Cells for the Treatment of Cancer

  • Manuel RamírezEmail author
  • Javier García Castro
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 6)


Mesenchymal stem cells (MSCs) may be used for treating patients with cancers. Several groups are developing different strategies exploiting the capacity of intravenously infused MSCs for targeting tumors, and their ability for carrying and delivering anticancer molecules. In this chapter we will present a summary on the works that have addressed the possibilities and potentials of MSCs as therapeutic elements against tumors, underscoring the implications for patients suffering from cancers.


Vascular Endothelial Growth Factor Mesenchymal Stem Cell Migration Inhibitory Factor Oncolytic Virus Brain Stem Glioma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alm JJ, Koivu HM, Heino TJ, Hentunen TA, Laitinen S, Aro HT (2010) Circulating plastic adherent mesenchymal stem cells in aged hip fracture patients. J Orthop Res 28:1634–1642PubMedCrossRefGoogle Scholar
  2. Barti-Juhasz H, Mihalik R, Nagy K, Grisendi G, Dominici M, Petak I (2011) Bone marrow derived mesenchymal stem/stromal cells transduced with full length human TRAIL repress the growth of rhabdomyosarcoma cells in vitro. Haematologica 96:e21–e22PubMedCrossRefGoogle Scholar
  3. Bexell D, Scheding S, Bengzon J (2010) Toward brain tumor gene therapy using multipotent mesenchymal stromal cell vectors. Mol Ther 18:1067–1075PubMedCrossRefGoogle Scholar
  4. Bui KC, Senadheera D, Wang X, Hendrickson B, Friedlich P, Lutzko C (2010) Recovery of multipotent progenitors from the peripheral blood of patients requiring extracorporeal membrane oxygenation support. Am J Respir Crit Care Med 181:226–237PubMedCrossRefGoogle Scholar
  5. Choi SA, Hwang SK, Wang KC, Cho BK, Phi JH, Lee JY, Jung HW, Lee DH, Kim SK (2011) Therapeutic efficacy and safety of TRAIL-producing human adipose tissue-derived mesenchymal stem cells against experimental brainstem glioma. Neuro Oncol 13:61–69PubMedCrossRefGoogle Scholar
  6. Ciavarella S, Dominici M, Dammacco F, Silvestris F (2011) Mesenchymal stem cells: a new promise in anticancer therapy. Stem Cells Dev 20:1–10PubMedCrossRefGoogle Scholar
  7. Compte M, Cuesta AM, Sánchez-Martín D, Alonso-Camino V, Vicario JL, Sanz L, Alvarez-Vallina L (2009) Tumor immunotherapy using gene-modified human mesenchymal stem cells loaded into synthetic extracellular matrix scaffolds. Stem Cells 27:753–760PubMedCrossRefGoogle Scholar
  8. Corsten MF, Shah K (2008) Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol 9:376–384PubMedCrossRefGoogle Scholar
  9. Dwyer RM, Potter-Beirne SM, Harrington KA, Lowery AJ, Hennessy E, Murphy JM, Barry FP, O’Brien T, Kerin MJ (2007) Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res 13:5020–5027PubMedCrossRefGoogle Scholar
  10. Francois S, Bensidhoum M, Mouiseddine M, Mazurier C, Allenet B, Semont A, Frick J, Sache A, Bouchet S, Thierry D, Gourmelon P, Gorin NC, Chapel A (2006) Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage. Stem Cells 24:1020–1029PubMedCrossRefGoogle Scholar
  11. Friedenstein AJ, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403PubMedGoogle Scholar
  12. García-Castro J, Alemany R, Cascalló M, Martínez-Quintanilla J, Arriero Mdel M, Lassaletta A, Madero L, Ramírez M (2010) Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study. Cancer Gene Ther 17:476–483PubMedCrossRefGoogle Scholar
  13. García-Gómez I, Elvira G, Zapata AG, Lamana ML, Ramírez M, Castro JG, Arranz MG, Vicente A, Bueren J, García-Olmo D (2010) Mesenchymal stem cells: biological properties and clinical applications. Expert Opin Biol Ther 10:1453–1468PubMedCrossRefGoogle Scholar
  14. Goldberg ED, Dygai AM, Zhdanov VV, Zyuzkov GN, Guryantseva LA, Pershina OV, Poveteva TN, Stavrova LA, Khrichkova TY (2006) Participation of mesenchymal precursor cells in wound healing on skin flap model. Bull Exp Biol Med 142:116–118PubMedCrossRefGoogle Scholar
  15. Grisendi G, Bussolari R, Cafarelli L, Petak I, Rasini V, Veronesi E, De Santis G, Spano C, Tagliazzucchi M, Barti-Juhasz H, Scarabelli L, Bambi F, Frassoldati A, Rossi G, Casali C, Morandi U, Horwitz EM, Paolucci P, Conte P, Dominici M (2010) Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res 70:3718–3729PubMedCrossRefGoogle Scholar
  16. Gunnarsson S, Bexell D, Svensson A, Siesjö P, Darabi A, Bengzon J (2010) Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFNgamma-transduced tumor cell immunotherapy of experimental glioma. J Neuroimmunol 218:140–144PubMedCrossRefGoogle Scholar
  17. Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, Zhu Z, Hicklin DJ, Okumura K, Ogawa H, Werb Z, Hattori K (2005) Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J Exp Med 202:739–750PubMedCrossRefGoogle Scholar
  18. Ho IA, Chan KY, Ng WH, Guo CM, Hui KM, Cheang P, Lam PY (2009) Matrix metalloproteinase 1 is necessary for the migration of human bone marrow-derived mesenchymal stem cells toward human glioma. Stem Cells 27:1366–1375PubMedCrossRefGoogle Scholar
  19. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC (2004) Gastric cancer originating from bone marrow-derived cells. Science 306:1568–1571PubMedCrossRefGoogle Scholar
  20. Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ (2007) Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS One 2:e416PubMedCrossRefGoogle Scholar
  21. Karp JM, Leng Teo GS (2009) Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4:206–216PubMedCrossRefGoogle Scholar
  22. Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, Cox JD, Andreeff M, Marini FC (2007) Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res 67:11687–11695PubMedCrossRefGoogle Scholar
  23. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F (2011) Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells 29:11–19PubMedCrossRefGoogle Scholar
  24. Komarova S, Kawakami Y, Stoff-Khalili MA, Curiel DT, Pereboeva L (2006) Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol Cancer Ther 5:755–766PubMedCrossRefGoogle Scholar
  25. Kosztowski T, Zaidi HA, Quinones-Hinojosa A (2009) Applications of neural and mesenchymal stem cells in the treatment of gliomas. Expert Rev Anticancer Ther 9:597–612PubMedCrossRefGoogle Scholar
  26. Laconi E (2007) The evolving concept of tumor microenvironments. Bioessays 29:738–744PubMedCrossRefGoogle Scholar
  27. Li Y, Yu X, Lin S, Li X, Zhang S, Song YH (2007) Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells. Biochem Biophys Res Commun 356:780–784PubMedCrossRefGoogle Scholar
  28. Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65:3307–3318PubMedGoogle Scholar
  29. Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, Bizen A, Honmou O, Niitsu Y, Hamada H (2004) Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther 11:1155–1164PubMedCrossRefGoogle Scholar
  30. Ponte AL, Marais E, Gallay N, Langonné A, Delorme B, Hérault O, Charbord P, Domenech J (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25:1737–1745PubMedCrossRefGoogle Scholar
  31. Ramírez M, Lucia A, Gómez-Gallego F, Esteve-Lanao J, Pérez-Martínez A, Foster C, Andreu AL, Martin MA, Madero L, Arenas J, García-Castro J (2006) Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury. Br J Sports Med 40:719–722PubMedCrossRefGoogle Scholar
  32. Roth JC, Curiel DT, Pereboeva L (2008) Cell vehicle targeting strategies. Gene Ther 15:716–729PubMedCrossRefGoogle Scholar
  33. Ryu CH, Park SH, Park SA, Kim SM, Lim JY, Jeong CH, Yoon WS, Oh WI, Sung YC, Jeun SS (2011) Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells. Hum Gene Ther 22:733–743PubMedCrossRefGoogle Scholar
  34. Schichor C, Birnbaum T, Etminan N, Schnell O, Grau S, Miebach S, Aboody K, Padovan C, Straube A, Tonn JC, Goldbrunner R (2006) Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol 199:301–310PubMedCrossRefGoogle Scholar
  35. Schmidt A, Ladage D, Schinkothe T, Klausmann U, Ulrichs C, Klinz FJ, Brixius K, Arnhold S, Desai B, Mehlhorn U, Schwinger RH, Staib P, Addicks K, Bloch W (2006) Basic fibroblast growth factor controls migration in human mesenchymal stem cells. Stem Cells 24:1750–1758PubMedCrossRefGoogle Scholar
  36. Seo SH, Kim KS, Park SH, Suh YS, Kim SJ, Jeun SS, Sung YC (2011) The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity. Gene Ther 18:488–495PubMedCrossRefGoogle Scholar
  37. Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F (2008) Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther 15:730–738PubMedCrossRefGoogle Scholar
  38. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62:3603–3608PubMedGoogle Scholar
  39. Tomchuck SL, Zwezdaryk KJ, Coffelt SB, Waterman RS, Danka ES, Scandurro AB (2007) Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells 26:99–107PubMedCrossRefGoogle Scholar
  40. Wang H, Cao F, De A, Cao Y, Contag C, Gambhir SS, Wu JC, Chen X (2009) Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem Cells 27:1548–1558PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Oncohematología y TrasplanteHospital Universitario Niño JesúsMadridSpain

Personalised recommendations