Concise Review: Genetically Engineered Stem Cell Therapy Targeting Angiogenesis and Tumor Stroma in Gastrointestinal Malignancy

Cell-based gene therapy holds considerable promise for the treatment of human malignancy. Genetically engineered cells if delivered to sites of disease could alleviate symptoms or even cure cancer through expression of therapeutic or suicide transgene products. Mesenchymal stem cells (MSCs), nonhematopoietic multipotent cells found primarily in bone marrow, have garnered particular interest as potential tumor-targeting vehicles due to their innate tumortropic homing properties. However, recent strategies go further than simply using MSCs as vehicles and use the stem cell-specific genetic make-up to restrict transgene expression to tumorigenic environments using tumor-tissue specific promoters. This addresses one of the concerns with this novel therapy that nonselective stem cell-based therapy could induce cancer rather than treat it. Even minimal off-target effects can be deleterious, motivating recent strategies to not only enhance MSC homing but also engineer them to make their antitumor effect selective to sites of malignancy. This review will summarize the advances made in the past decade toward developing novel cell-based cancer therapies using genetically engineered MSCs with a focus on strategies to achieve and enhance tumor specificity and their application to targeting gastrointestinal malignancies such as hepatocellular carcinoma and pancreatic adenocarcinoma. STEM CELLS 2013;31:227-235