Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo

Salmasi, Zahra; Hashemi, Maryam; Mahdipour, Elahe; Nourani, Hossein; Abnous, Khalil; Ramezani, Mohammad

doi:10.1002/btpr.3025

Cited by 20 publications

(11 citation statements)

References 49 publications

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“…Efficient migration to tumor tissue resulted in delayed tumor proliferation in xenografts (Nieddu et al, 2019) Lung carcinoma Significant abrogation of tumor growth in A549 cell-bearing mice (Mohr et al, 2008;Yan et al, 2016) Breast cancer Inducing the apoptosis of MCF-7 cells in vitro (Khorashadizadeh et al, 2015) Several tumors Abrogation of breast, lung, and cervical cancer cell growth in vitro and in vivo (Loebinger et al, 2009) Melanoma Suppressing tumor growth in B16F0 cells bearing murine (Salmasi et al, 2020) Hepatocellular carcinoma…”

Section: Neuroblastomamentioning

confidence: 99%

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

Hassanzadeh

Altajer²,

Rahman

et al. 2021

Front. Cell Dev. Biol.

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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.

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Section: Neuroblastomamentioning

confidence: 99%

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

Hassanzadeh

Altajer²,

Rahman

et al. 2021

Front. Cell Dev. Biol.

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“…MSCs at Passage 3 were cultured in 12‐well plates with a density of 4 × 10 4 cells per well and the media were refeeded every 2–3 days. Twenty‐one days later, lipid droplets were stained by Oil Red O solution (Santa Cruz, CA) 14,15 …”

Section: Methodsmentioning

confidence: 99%

Evaluation of the efficiency of modified PAMAM dendrimer with low molecular weight protamine peptide to deliver IL ‐12 plasmid into stem cells as cancer therapy vehicles

Azimifar

Salmasi

Doosti

et al. 2021

Biotechnol Progress

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Interleukin 12 (IL-12) is considered as an important molecule for cancer immunotherapy with significant roles in hindering tumor activity, mostly mediated by tumorassociated macrophages and anti-angiogenic factors. Mesenchymal stem cells (MSCs) have been come out as promising carriers to increase the accumulation of drug/gene in tumor sites. As a vehicle, MSCs have various advantages, including tumor-specific propensity and migratory ability; however, they have limited transfection efficiency, compared to other cells. In this study, we introduced a novel delivery system based on poly-(amidoamine) (PAMAM) (G5) to deliver a plasmid encoding IL-12 to MSCs. Initially, 30% of the amine surface of PAMAM was substituted by 10-bromodecanoic acid. Then, the low molecular weight of protamine peptide was conjugated to PAMAM and PAMAM-alkyl with N-succinimidyl 3-(2-pyridyldithio) propionate as a linker. Physicochemical properties of this modified PAMAM were evaluated, including size and surface charge, toxicity, transfection efficiency to deliver reporter and IL-12 genes into MSCs and finally the migration potential of the engineered stem cells into cancer and normal cell lines (HepG2 and NIH/3 T3). The results showed that alkyl-peptide modified PAMAM with low toxicity had a higher potential to deliver green fluorescent protein and IL-12 genes to stem cells, than PMAMAM, PAMAMalkyl and PAMAM-peptide. These engineered stem cells had a greater ability to migrate to cancer cells than normal cells. It can be concluded that engineered stem cells containing the IL-12 gene can be considered as an efficient cell carrier for cancer immunotherapy. Further clinical studies are needed to confirm these results.

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“…Mesenchymal stem cells are also engineered to express membrane-bound TRAIL in its natural form. The exosomes derived from such cells, or the cells themselves have been used to deliver TRAIL to tumor [ 126 , 127 , 128 , 129 ]. These strategies not only provide the natural form of TRAIL, but also take advantage of the special “homing” properties of mesenchymal stem cells to deliver TRAIL to tumor sites.…”

Section: Future Perspective and Summarymentioning

confidence: 99%

Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma

You

Nguyen

et al. 2021

IJMS

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Melanoma as a very aggressive type of cancer is still in urgent need of improved treatment. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and arginine deiminase (ADI-PEG20) are two of many suggested drugs for treating melanoma. Both have shown anti-tumor activities without harming normal cells. However, resistance to both drugs has also been noted. Studies on the mechanism of action of and resistance to these drugs provide multiple targets that can be utilized to increase the efficacy and overcome the resistance. As a result, combination strategies have been proposed for these drug candidates with various other agents, and achieved enhanced or synergistic anti-tumor effect. The combination of TRAIL and ADI-PEG20 as one example can greatly enhance the cytotoxicity to melanoma cells including those resistant to the single component of this combination. It is found that combination treatment generally can alter the expression of the components of cell signaling in melanoma cells to favor cell death. In this paper, the signaling of TRAIL and ADI-PEG20-induced arginine deprivation including the main mechanism of resistance to these drugs and exemplary combination strategies is discussed. Finally, factors hampering the clinical application of both drugs, current and future development to overcome these hurdles are briefly discussed.

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Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo

Cited by 20 publications

References 49 publications

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

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

Evaluation of the efficiency of modified PAMAM dendrimer with low molecular weight protamine peptide to deliver IL ‐12 plasmid into stem cells as cancer therapy vehicles

Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma

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