Skip to main content
SpringerLink
Log in

Use of Bone Marrow Mesenchymal Stem Cells as Tumor Specific Delivery Vehicles

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 9

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 9))

  • 1346 Accesses

Abstract

Eradication of cancer, especially when it has metastasized is extremely difficult and conventional cancer therapies are simply unable to specifically target tumors/cancers, thus causing unwanted side effects and complications. Recently, it has been shown that bone marrow mesenchymal stem cells (MSCs) are able to migrate specifically to tumors and contribute to the formation of tumor-associated stroma. These properties make MSCs good candidates as anti-tumor agent delivery vehicles and lead to a great deal of interest in the possibility of genetically modifying MSCs to express anticancer molecules and using them as specific targeted anticancer agents. In this chapter, we will review the biological properties of MSCs and the contribution of MSCs in tumor establishment. The potential therapeutic applications of MSCs in the treatment of tumor using different MSCs-delivered anticancer agents will also be reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • 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. Mol Ther 17:183–190

    Article  PubMed  CAS  Google Scholar 

  • Cavarretta IT, Altanerova V, Matuskova M, Kucerova L, Culig Z, Altaner C (2010) Adipose tissue-derived mesenchymal stem cells expressing prodrug-converting enzyme inhibit human prostate tumor growth. Mol Ther 18:223–231

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Lin X, Zhao J, Shi W, Zhang H, Wang Y, Kan B, Du L, Wang B, Wei Y, Liu Y, Zhao X (2008) A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs. Mol Ther 16:749–756

    Article  PubMed  CAS  Google Scholar 

  • Cheng Z, Ou L, Zhou X (2008) Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance. Mol Ther 16:571e9

    Article  Google Scholar 

  • Cogle CR, Theise ND, Fu D, Ucar D, Lee S, Guthrie SM, Lonergan J, Rybka W, Krause DS, Scott EW (2007) Bone marrow contributes to epithelial cancers in mice and humans as developmental mimicry. Stem Cells 25:1881–1887

    Article  PubMed  Google Scholar 

  • Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA (2004) Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 64:8492–8495

    Article  PubMed  CAS  Google Scholar 

  • Duan X, Guan H, Cao Y, Kleinerman ES (2009) Murinebone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors. Cancer 115:13–22

    Article  PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247

    Article  PubMed  CAS  Google Scholar 

  • 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 70:3718–3729

    Article  PubMed  CAS  Google Scholar 

  • Gunnarsson S, Bexell D, Svensson A, Siesjö P, Darabi A, Bengzon J (2010) Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFN gamma-transduced tumor cell immunotherapy of experimental glioma. J Neuroimmunol 218:140–144

    Article  PubMed  CAS  Google Scholar 

  • Hall B, Andreeff M, Marini F (2007) The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol 180:263–283

    Article  PubMed  CAS  Google Scholar 

  • Kanehira M, Xin H, Hoshino K, Maemondo M, Mizuguchi H, Hayakawa T, Matsumoto K, Nakamura T, Nukiwa T, Saijo Y (2007) Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. Cancer Gene Ther 14:894–903

    Article  PubMed  CAS  Google Scholar 

  • Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, Battula VL, Weil M, Andreeff M, Marini FC (2009) Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 27:2614–2623

    Article  PubMed  CAS  Google Scholar 

  • Kim SM, Lim JY, Park SI, Jeong CH, Oh JH, Jeong M, Oh W, Park SH, Sung YC, Jeun SS (2008) Gene therapy using TRAIL secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res 68:9614–9623

    Article  PubMed  CAS  Google Scholar 

  • Kucerova L, Matuskova M, Pastorakova A, Tyciakova S, Jakubikova J, Bohovic R, Altanerova V, Altaner C (2008) Cytosine deaminase expressing human mesenchymal stem cells mediated tumour regression in melanoma bearing mice. J Gene Med 10:1071–1082

    Article  PubMed  CAS  Google Scholar 

  • Loebinger MR, Janes SM (2010) Stem cells as vectors for antitumour therapy. Thorax 65:362–369

    Article  PubMed  Google Scholar 

  • Loebinger MR, Eddaoudi A, Davies D, Janes SM (2009) Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res 69:4134–4142

    Article  PubMed  CAS  Google Scholar 

  • Menon LG, Kelly K, Yang HW, Kim SK, Black PM, Carroll RS (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

    Article  PubMed  CAS  Google Scholar 

  • Mohr A, Albarenque SM, Deedigan L, Yu R, Reidy M, Fulda S, Zwacka RM (2010) Targeting of XIAP combined with systemic mesenchymal stem cell-mediated delivery of sTRAIL ligand inhibits metastatic growth of pancreatic carcinoma cells. Stem Cells 28:2109–2120

    Article  PubMed  CAS  Google Scholar 

  • Mueller LP, Luetzkendorf J, Widder M, Nerger K, Caysa H, Mueller T (2011) TRAIL-transduced multipotent mesenchymal stromal cells (TRAIL-MSC) overcome TRAIL resistance in selected CRC cell lines in vitro and in vivo. Cancer Gene Ther 18:229–239

    Article  PubMed  CAS  Google Scholar 

  • 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 65:3307–3318

    PubMed  CAS  Google Scholar 

  • 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 11:1155–1164

    Article  PubMed  CAS  Google Scholar 

  • Ren C, Kumar S, Chanda D, Kallman L, Chen J, Mountz JD, Ponnazhagan S (2008) Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model. Gene Ther 15:1446–1453

    Article  PubMed  CAS  Google Scholar 

  • Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen S, Water JA, vande Mohapatra G, Figueiredo JL, Martuza RL, Weissleder R, Shah K (2009) Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 106:4822–4827

    Article  PubMed  CAS  Google Scholar 

  • Sato H, Kuwashima N, Sakaida T, Hatano M, Dusak JE, Fellows-Mayle WK, Papworth GD, Watkins SC, Gambotto A, Pollack IF, Okada H (2005) Epidermal growth factor receptor transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors. Cancer Gene Ther 12:757–768

    Article  PubMed  CAS  Google Scholar 

  • Song C, Xiang J, Tang J, Hirst DG, Zhou J, Chan KM, Li G (2011) Thymidine kinase gene modified bone marrow mesenchymal stem cells as vehicles for antitumor therapy. Hum Gene Ther 22:439–449

    Article  PubMed  CAS  Google Scholar 

  • Spaeth EL, Dembinski JL, Sasser AK, 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

    Article  PubMed  Google Scholar 

  • 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 62:3603–3608

    PubMed  CAS  Google Scholar 

  • Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, Champlin RE, Andreeff M (2004) Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 96:1593–1603

    Article  PubMed  CAS  Google Scholar 

  • 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. Mol Med 17:579–587

    Article  PubMed  CAS  Google Scholar 

  • 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 Cell 27:1548–1558

    Article  CAS  Google Scholar 

  • Xiang J, Tang J, Song C, Yang Z, Hirst DG, Zheng QJ, Li G (2009) Mesenchymal stem cells as a gene therapy carrier for treatment of fibrosarcoma. Cytotherapy 11:516–526

    Article  PubMed  CAS  Google Scholar 

  • Xin H, Kanehira M, Mizuguchi H, Hayakawa T, Kikuchi T, Nukiwa T, Saijo Y (2007) Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells. Stem Cells 25:1618–1626

    Article  PubMed  CAS  Google Scholar 

  • Xu G, Jiang XD, Xu Y, Zhang J, Huang FH, Cheu ZZ, Zhou DX, Shang JH, Zou YX, Cai YQ, Kou SB, Chen YZ, LU RX, Zeng YJ (2009) Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the grouth of glioma in rats. Cell Biol. Int 33:466–474.

    Article  Google Scholar 

  • Zischek C, Niess H, Ischenko I, Conrad C, Huss R, Jauch KW, Nelson PJ, Bruns C (2009) Targeting tumor stroma using engineered mesenchymal stem cells reduces the growth of pancreatic carcinoma. Ann Surg 250:747–753

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

This work is supported by a grant from National Natural Science Foundation of China (NSFC No.81172177) to Li Gang.

Author information

Authors and Affiliations

  1. Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, People’s Republic of China

    Ting Zhang

  2. Stem Cells and Regeneration Program, School of Biomedical Sciences and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, People’s Republic of China

    Gang Li

Authors
  1. Ting Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gang Li .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Zhang, T., Li, G. (2013). Use of Bone Marrow Mesenchymal Stem Cells as Tumor Specific Delivery Vehicles. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 9. Stem Cells and Cancer Stem Cells, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5645-8_19

Download citation

Publish with us

Policies and ethics

Search

Navigation