UC Davis

Current chemotherapy is not tumor-selective and gives rise to severe adverse effects for patients. Mesenchymal stem cells (MSCs) exhibit a unique tumor-homing property and could be used as a drug carrier for targeting tumor therapy. The tumor-homing property of MSCs depends on the hypoxia and inflammatory status in the tumor, and is modulated by factors such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) or other cytokines released from tumors. MSCs may be isolated from umbilical cord blood or adipose tissues, and are readily engineered for carrying therapeutics, such as oncolytic adenovirus, specific cytotoxic molecules, nucleotides, prodrugs cytokines or antibodies, or to produce therapeutic molecules within a tumor site. The most promising therapeutics include blockers for VEGF, prodrugs (e.g. ganciclovir), oncolytic adenovirus, thymidine kinase, and pro-apoptotic “TRAIL”. The efficacy of these bio-engineered MSCs has been evaluated in animal models of pulmonary, breast, gastrointestinal, and pancreatic cancer xenografts grown in immune-deficient mice, and their safety has been shown in some early phase human trials, but they have yet not been moved to later phase clinical application. Although these novel approaches are promising, MSCs may have some risks for cancer patients since MSCs are found to be immunosuppressive in tumor sites, are pro-angiogenic, and in some cases may promote tumor growth. Therefore, whether bio-engineered MSCs will be a useful therapeutic vehicle depends on the property of the specially engineered cell population, tumor types and locations, as well as the time and route of administration of MSCs-based therapeutics. This chapter discusses approaches to utilize MSCs’ tumor-homing properties for improving current cancer therapy.