RETRACTED: Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy

Abstract

Mesenchymal stem/stromal cell (MSC)-based therapy has become an attractive and advanced scientific research area in the context of cancer therapy. This interest is closely linked to the MSC-marked tropism for tumors, suggesting them as a rational and effective vehicle for drug delivery for both hematological and solid malignancies. Nonetheless, the therapeutic application of the MSCs in human tumors is still controversial because of the induction of several signaling pathways largely contributing to tumor progression and metastasis. In spite of some evidence supporting that MSCs may sustain cancer pathogenesis, increasing proofs have indicated the suppressive influences of MSCs on tumor cells. During the last years, a myriad of preclinical and some clinical studies have been carried out or are ongoing to address the safety and efficacy of the MSC-based delivery of therapeutic agents in diverse types of malignancies. A large number of studies have focused on the MSC application as delivery vehicles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), chemotherapeutic drug such as gemcitabine (GCB), paclitaxel (PTX), and doxorubicin (DOX), prodrugs such as 5-fluorocytosine (5-FC) and ganciclovir (GCV), and immune cell-activating cytokines along with oncolytic virus. In the current review, we evaluate the latest findings rendering the potential of MSCs to be employed as potent gene/drug delivery vehicle for inducing tumor regression with a special focus on the in vivo reports performed during the last two decades.

RETRACTED: Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy

“…The strong tumor tropism of MSCs makes them reliable candidates as gene delivery vehicles, providing sustained and continued releases of antitumor cytokine. Based on the recent reports, MSCs can unfavorably support tumor progress by a diversity of mechanisms, containing the stimulation of drug resistance, proangiogenic functions, and eliciting metastasis procedure by stimulation of epithelial-mesenchymal transition (EMT) and also enrichments of the cancer stem cell (CSC) niche (139,140). MSC-derived factors are reliable for the listed unwanted effects, affecting the various hallmarks of cancer.…”

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

“…Additionally, the immunosuppressive effect of MSC contributes to cancer cells’ escape from the immune system surveillance. Due to their direct action on immune cells, MSCs are capable of inhibiting apoptosis or inhibition of T cell proliferation which results in a decline of immunogenic activity [ 16 ]. Furthermore, MSC has also shown pro-metastatic effects that are mediated via paracrine factors, including TGF-β, CXCR4, and CCL5; chemokines secreted from MSC [ 10 , 16 , 17 ].…”

“…Due to their direct action on immune cells, MSCs are capable of inhibiting apoptosis or inhibition of T cell proliferation which results in a decline of immunogenic activity [ 16 ]. Furthermore, MSC has also shown pro-metastatic effects that are mediated via paracrine factors, including TGF-β, CXCR4, and CCL5; chemokines secreted from MSC [ 10 , 16 , 17 ]. Martin et al (2010) revealed that the co-culture of bone marrow-derived MSC with breast cancer resulted in the overexpression of EMT-specific genes and a decrease of mesenchymal to epithelial (MET) genes [ 18 ].…”

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

“…While the focus of this paper is on the optimization of current NC-based systems in targeting stem cell markers and pathways, alternative CSC applications like CSCs as vehicles of delivery [ 238 , 334 , 335 ] or even infused stem therapy [ 336 ] cannot be dismissed. As such, MSCs in the context of therapeutic carriers are gaining rapid popularity as a strategy to ensure ameliorated side-effects on account of improved biocompatibility [ 332 , 337 ].…”