Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Abstract

Introduction: Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene-or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered: In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion: Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

HCV Interplay With Mir34a: Implications in Hepatocellular Carcinoma

“…Likely, our results provide insights on the cytostatic/cytotoxic effect of HCV infection in neoplastic cells ( Figure S1 B ). On the other hand, this investigation may open a route for a novel therapeutic intervention based on EVs loaded with miR34, or engineered cells, such as MSCs ( 50 ), able to release this miRNA by EV delivery (data not shown) for their tumor tropism ( 51 ), thus reducing tumor progression. Further studies are needed to confirm this strategy for HCC prevention after HCV eradication.…”

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…Among their broad applications, EVs are sometimes utilized based on their nano-sized features and ability to pass through blood barriers ( 136 ). In such cases, EVs could be applied as a new paradigm with amenable priorities ( 137 , 138 ). EVs can achieve most features of the synthetic nano-carriers (i.e., liposomes and nano-particles).…”

Stem Cells for Cancer Therapy: Translating the Uncertainties and Possibilities of Stem Cell Properties into Opportunities for Effective Cancer Therapy

“…As such, it is evident that for MSC-based cancer therapy to remain applicable and relevant as a mainstream cancer therapy, a more homogenous form of MSCs with specific tumor-homing activity and more efficient drug delivery strategies to cancer cells are needed. [ 66 , 67 ] Although much is still unknown about the mechanisms by which exosomes and their miRNA interact with tumors, the advancement of gene engineering techniques provides opportunities to further develop these nano-size vesicles with improved targeting specificity for the delivery of anti-oncomirs [ 68 ]. For instance, exosomes have been shown to possess homing capabilities similar to that of MSC from which they were derived, and genetic modifications of membrane proteins on the exosomal surface could enhance its tumor targeting properties allowing the interaction of anti-oncomirs to be delivered in a more targeted manner [ 69 ].…”