Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer

Details

• Alternative Title:
  Biomaterials
• Personal Author:
  Yin, Perry T. ; Shah, Shreyas ; Pasquale, Nicholas J. ; Garbuzenko, Olga B. ; Minko, Tamara ; Lee, Ki-Bum
• Description:
  Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo.
• Subjects:
  Animals Apoptosis Article Cancer Therapy Cell Differentiation Cell Line, Tumor Cell Movement Cell Proliferation Female Gene Therapy Genetic Therapy Hot Temperature Humans Hyperthermia Hyperthermia, Induced Magnetic Core-shell Nanoparticles Magnetics Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells Mice, Nude Nanoparticles Ovarian Neoplasms Plasmids Polyethyleneimine Stem Cell Therapy TNF-Related Apoptosis-Inducing Ligand

  More +
• Source:
  Biomaterials. 81:46-57.
• Pubmed ID:
  26720500
• Pubmed Central ID:
  PMC4715938
• Document Type:
  Journal Article
• Funding:
  DP2 OD006462/OD/NIH HHS/United States ; R21 NS085569/NS/NINDS NIH HHS/United States ; R21NS0855691/NS/NINDS NIH HHS/United States ; R01 CA138533/CA/NCI NIH HHS/United States ; T32 GM008339/GM/NIGMS NIH HHS/United States ; 1DP20D006462-01/DP/NCCDPHP CDC HHS/United States ; T32 GM8339/GM/NIGMS NIH HHS/United States ; R01CA138533/CA/NCI NIH HHS/United States
• Volume:
  81
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:996054b485eb3e3ecd6b232c86909dbec7a3a6fc54c3dc22d1564ac56279d919
• Download URL:
  https://stacks.cdc.gov/view/cdc/39430/cdc_39430_DS1.pdf
• File Type:
  [PDF - 2.13 MB ]