Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy

Cancer Res. 2010 May 1;70(9):3718-29. doi: 10.1158/0008-5472.CAN-09-1865. Epub 2010 Apr 13.


Adipose-derived mesenchymal stromal/stem cells (AD-MSC) may offer efficient tools for cell-based gene therapy approaches. In this study, we evaluated whether AD-MSC could deliver proapoptotic molecules for cancer treatment. Human AD-MSCs were isolated and transduced with a retroviral vector encoding full-length human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a proapoptotic ligand that induces apoptosis in a variety of human cancers but not normal tissues. Although several studies have documented the antitumor activity of recombinant human TRAIL, its use in vivo is limited by a short half-life in plasma due to a rapid clearance by the kidney. We found that these limitations can be overcome using stably transduced AD-MSC, which could serve as a constant source of TRAIL production. AD-MSC armed with TRAIL targeted a variety of tumor cell lines in vitro, including human cervical carcinoma, pancreatic cancer, colon cancer, and, in combination with bortezomib, TRAIL-resistant breast cancer cells. Killing activity was associated with activation of caspase-8 as expected. When injected i.v. or s.c. into mice, AD-MSC armed with TRAIL localized into tumors and mediated apoptosis without significant apparent toxicities to normal tissues. Collectively, our results provide preclinical support for a model of TRAIL-based cancer therapy relying on the use of adipose-derived mesenchymal progenitors as cellular vectors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / physiology*
  • Animals
  • Apoptosis / physiology
  • Boronic Acids / pharmacology
  • Bortezomib
  • Caspase 8 / metabolism
  • Cell Communication / physiology
  • Coculture Techniques
  • Enzyme Activation
  • Female
  • HeLa Cells
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred NOD
  • Pyrazines / pharmacology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage*
  • TNF-Related Apoptosis-Inducing Ligand / biosynthesis
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • Transduction, Genetic
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*


  • Boronic Acids
  • Pyrazines
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Bortezomib
  • Caspase 8