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.
Highlights
There is a rapidly evolving interest in the marked competencies of the cell-based approach for amelioration of a myriad of pathological conditions ranging from degenerative disorders to cancers (Ramdasi et al, 2015; Wang M. et al, 2018)
Investigation of the immune response to Mesenchymal stem/stromal cell (MSC) loaded with oncolytic adenovirus (MSC-oAd) using the semipermissive cotton rat (CR) model verified that CR-MSCs could sustain the replication of oncolytic adenovirus in vitro (Ahmed et al, 2010)
In 2010, evaluation of the safety and the efficacy of injection of autologous MSCs transduced with ICOVIR-5, a new oAd, in four children with metastatic neuroblastoma demonstrated that the injection was well tolerated; on the other hand, a complete clinical response was verified in one participant, describing MSCs as eligible vehicles for oncolytic virus delivery into metastatic tumors with very low systemic toxicity concomitant with reliable antitumor effects (García-Castro et al, 2010)
Summary
There is a rapidly evolving interest in the marked competencies of the cell-based approach for amelioration of a myriad of pathological conditions ranging from degenerative disorders to cancers (Ramdasi et al, 2015; Wang M. et al, 2018). A unique characteristic of MSCs is their lower immunogenicity due to the lack of expression of costimulatory molecules (Najar et al, 2012; Wu et al, 2014), which eliminates the need for using immunosuppressive agents postallogeneic transplantation This characteristic makes them supremely appropriate for cell-based cancer immunotherapy as either gene or drug delivery vehicles (Le Blanc and Ringden, 2006; Kean et al, 2013; Nasr et al, 2015). Systemic injection of BM-MSCs transduced with a recombinant adenoviral vector expressing the murine IL-12 in a 786-0 renal cell carcinoma (RCC)-bearing mice supported the delayed tumor growth and significantly sustained mouse survival following homing to tumors and production of local IL-12 (Gao et al, 2010). In addition to the evidenced therapeutic efficacy of IL-12-producing BM-MSCs in Ewing sarcoma tumors (Duan et al, 2009), another study revealed their
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