Mesenchymal stem cells engineered for cancer therapy

Abstract

Recent pre-clinical and clinical studies have shown that stem cell-based therapies hold tremendous promise for the treatment of human disease. Mesenchymal stem cells (MSC) are emerging as promising anti-cancer agents which have an enormous potential to be utilized to treat a number of different cancer types. MSC have inherent tumor-trophic migratory properties, which allows them to serve as vehicles for delivering effective, targeted therapy to isolated tumors and metastatic disease. MSC have been readily engineered to express anti-proliferative, pro-apoptotic, anti-angiogenic agents that specifically target different cancer types. Many of these strategies have been validated in a wide range of studies evaluating treatment feasibility or efficacy, as well as establishing methods for real-time monitoring of stem cell migration in vivo for optimal therapy surveillance and accelerated development. This review aims to provide an in depth status of current MSC-based cancer therapies, as well as the prospects for their clinical translation.

Cancer stem cell hypothesis: a brief summary and two proposals

“…Although the existence of stem cell niches has been identified in multiple mammalian tissues, we (Bjerkvig et al 2005). Most recent studies showed differentiated cancer cells could dedifferentiate spontaneously into cancer stem cells (Chaffer et al 2011) Cytotechnology (2013) (Shah 2012). However, the major hurdle that thwarts the clinical application of this strategy is the inherent uncertainty after the injection of these stem cells or MSCs.…”

Therapeutically targeting SELF‐reinforcing leukemic niches in acute myeloid leukemia: A worthy endeavor?

“…In addition, MSC exposure to toll-like ligand receptor-2 (TLR2) (peptidoglycan), the activation of TLR4 (lipopolysaccharide) [61] and exposure to platelet lysate supplemented media [124] might polarize microenvironmental MSCs toward a proinflammatory phenotype, but it is still doubtful whether this type of priming might be truly effective. Instead, the most exciting and clinically relevant finding is that MSCs possess unique tumor-trophic, drug-resistant and migratory properties and overexpress efflux transporters such as P-glycoproteins [125]. These features have founded the rationale to develop MSCs as vehicles to deliver specific anti-angiogenic and anti-tumor agents [127,128].…”

Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems

“…Different molecules can be a target site for antiangiogenic therapy due to their engagement in tumor-mediated angiogenesis [46] which gives possibility for use of MSCs expressing antiangiogenic factors (thrombospondin (TSP)-1) to inhibited tumor development [47][48][49].…”