|Genetically-modified MSCs home to tumor cells and|
accumulate at the tumor site. Image adapted from
In the body, MSCs are known to home to sites of acute injury and inflammation and migrate to tumors in response to tumor secretion of growth factors, cytokines, and extracellular matrix (ECM) molecules. However, given their secretion of biomolecules that augment new blood vessel formation, increase inflammation, and degrade the ECM (lending to tumor metastasis), MSCs may promote rather than impede tumor growth and migration, and confounding results from a number of in vitro and in vivo studies have been published to date. Furthermore, it has been suggested that the ability of MSCs to interact with malignant cells and cancer stem cells might preclude their safe therapeutic application, particularly in patients with dormant or undiagnosed cancers. Despite these concerns, MSCs can serve as an effective ‘Trojan Horse’ for the targeted delivery of anticancer genes, proteins and drugs to tumor cells. Such targeted delivery can reduce the unsavory systemic side effects that often result from the use of anti-cancer agents, reducing patient morbidity and improving quality of life.
MSCs can serve as an effective ‘Trojan Horse’ for the targeted delivery of anticancer genes, proteins and drugs to tumor cells.
Recently, a review was published focusing not only on the application of MSCs for the targeted delivery of anti-cancer agents to tumors, but also on the molecular mechanisms of MSC accumulation in tumors, a poorly understood mechanism. For MSC-based anti-cancer therapies to be effective clinically, these mechanisms must be understood and successfully exploited. The authors identified several methods to genetically-modify MSCs that resulted in tumor growth inhibition, metastasis suppression, and prolonged survival upon MSC injection in various tumor-laden animal models. However, in addition to modification with anti-cancer agents, MSCs must be able to accumulate at the site of the tumor for effective cancer eradication. The authors postulate that increasing the accumulation efficiency of MSCs at tumor sites can effectively target not only primary tumors but also metastatic lesions.