Cancer gene therapy using mesenchymal stem cells

Abstract

Cellular and gene therapies represent promising treatment strategies at the frontier of medicine. Hematopoietic stem cells, lymphocytes, and mesenchymal stem cells (MSCs) can all serve as sources of cells for use in such therapies. Strategies for gene therapy are often based on those of cell therapy, and it is anticipated that some examples will be put to practical use in the near future. Given their ability to support hematopoiesis, MSCs may be useful for the enhancement of stem cell engraftment, and the acceleration of hematopoietic reconstitution. Furthermore, MSCs may advance the treatment of severe graftversus-host disease, based on their immunosuppressive ability. This application is also based on the homing behavior of MSCs to sites of injury and inflammation. Interestingly, MSCs possess tumor-homing ability, opening up the possibility of applications in the targeted delivery of anti-cancer genes to tumors. Many reports have indicated that MSCs can be utilized to target tumors and to deliver anti-cancer molecules locally, as tumors are recognized as non-healing wounds with inflammatory tissue. Here, we review both the potential of MSCs as cellular vehicles for targeted cancer therapy and the molecular mechanisms underlying MSC accumulation at tumor sites.

Thyroid hormones and tetrac: new regulators of tumour stroma formation via integrin αvβ3

“…An array of growth factors, including PDGF, insulin-like growth factor 1 (IGF1), HGF, EGF and VEGF, as well as chemokines, such as RANTES/CCL5, CCL22 and, to a lower extent, SDF-1/CXCL12 and their respective receptors, have been implicated in MSC migration (Ponte et al 2007, Spaeth et al 2008) and many of these have been shown in this and other studies to be regulated by thyroid hormones via differential gene expression and receptor crosstalk (Davis et al 2011, Hercbergs et al 2012. Modulation of recruitment and engraftment efficiency of MSCs is of clinical interest, in settings of tissue regeneration, in the context of general tumour growth and the emerging field of MSC-based gene delivery in cancer therapy (Knoop et al 2011, Knoop et al 2013, Uchibori et al 2014. As the tumour stroma plays such a key role in tumour growth, angiogenesis and metastatic potential, it has become an important target for tumour therapy.…”

An Empirical Study of the Prescription Pattern of Drugs for Hematological Malignancies in Japan from 2010–2014

“…In this way, more and more molecularly targeted drugs are being developed for cancer therapies around the world, including in Japan. 3) In addition, gene therapy [4][5][6][7] and immunotherapy [8][9][10][11] have been developed for hematological malignancies, suggesting that the number of the treatment options will increase in the near future.…”

Stem Cell Transplantation for Traumatic Spinal Cord Injury: What Have We Learned from Previous Experience

“…Other mechanisms exclusively found with MSCs are immunomodulation (26,27) gene delivery (28)(29)(30) and angiogenesis (31)(32)(33). …”