Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

Krassikova, Lyudmila S.; Karshieva, Saida Sh; Cheglakov, I. B.; Belyavsky, A. V.

doi:10.1002/jgm.2894

Cited by 9 publications

(8 citation statements)

References 41 publications

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“…Melanoma 5-FC Marked inhibition of tumor growth with direct intratumoral transplantation of MSCs expressing CD followed by systemic injection of 5-FC in melanoma mice models (Krasikova et al, 2015) Osteosarcoma 5-FC Inhibition of the tumor growth in mice subcutaneously injected with osteosarcoma Cal72 cells following administration of stable CD/5-FC MSC cell line (NguyenThai et al, 2015) Lewis lung carcinoma 5-FC Significant inhibition of tumor growth with direct intratumoral transplantation of AT-MSCs expressing CD followed by systemic injection of 5-FC in mice models resulted in prolonged survival of treated mice (Krassikova et al, 2016 (Zischek et al, 2009) Lung melanoma metastasis GCV Significant reduction in tumor colonization resulted in amelioration in the survival of murine melanoma lung metastasis models following injection of MSCs expressing TK with GCV (Zhang et al, 2015) AT-MSCs, adipose tissue-derived mesenchymal stem/stromal cells; GCV, ganciclovir, CD, cytosine deaminase, 5-FC, 5-fluorocytosine; TK, thymidine kinase; CTLs, cytotoxic T lymphocytes; iPSCs, induced pluripotent stem cells.…”

Section: Cancer Prodrug Main Resultsmentioning

confidence: 99%

“…Furthermore, assessment of the bystander effect presented that the MSC-CD increased human osteosarcoma Cal72 cytotoxicity in co-culture condition in the existence of 5-FC; on the other hand, MSC-CD injection along with 5-FC suppressed tumor development compared with control mice in Cal72 cell-bearing mice (NguyenThai et al, 2015). Combination therapy with AT-MSCs expressing CD and lysomustine chemotherapy, a nitrosourea derivative of lysine, followed by systemic injection of 5-FC in mice bearing latestage Lewis lung carcinoma (LLC) led to the significant attenuation of tumor growth, as evidence by decreased tumor volume (Krassikova et al, 2016). Moreover, the intervention resulted in prolonged survival of transplanted mice.…”

Section: Cancer Prodrug Main Resultsmentioning

confidence: 99%

“…Combination therapy with AT-MSCs expressing CD and lysomustine chemotherapy, a nitrosourea derivative of lysine, followed by systemic injection of 5-FC in mice bearing late-stage Lewis lung carcinoma (LLC) led to the significant attenuation of tumor growth, as evidence by decreased tumor volume ( Krassikova et al, 2016 ). Moreover, the intervention resulted in prolonged survival of transplanted mice.…”

Section: Msc-based Delivery Of Prodrugsmentioning

confidence: 99%

“…Moreover, the intervention resulted in prolonged survival of transplanted mice. More significantly, combination therapy showed a higher antitumor effect in murine models compared with monotherapies with injected AT-MSC-CD or lysomustine alone ( Krassikova et al, 2016 ). Likewise, intratumoral transplantation of the iPS-derived MSCs expressing CD into a murine xenogeneic model of human breast cancer followed by 5-FC administration not only induced tumor regression but also diminished lung metastases ( Ullah et al, 2017 ).…”

Section: Msc-based Delivery Of Prodrugsmentioning

confidence: 99%

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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: Cancer Prodrug Main Resultsmentioning

confidence: 99%

Section: Cancer Prodrug Main Resultsmentioning

confidence: 99%

Section: Msc-based Delivery Of Prodrugsmentioning

confidence: 99%

Section: Msc-based Delivery Of Prodrugsmentioning

confidence: 99%

See 2 more Smart Citations

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

Hassanzadeh

Altajer²,

Rahman

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…There are various kinds of studies using different strategies and animal models to test the efficacy of engineered MSCs for the treatment of cancer/metastasis. In some studies, engineered MSCs were delivered after the tumors or metastatic lesions were established in animal models (Chen et al, 2008;Ren et al, 2008;Xin et al, 2009;Gao et al, 2010;Bak et al, 2011;Conrad et al, 2011;Zhang et al, 2011;Wang et al, 2012;Kim et al, 2013;Lee et al, 2013;Martinez-Quintanilla et al, 2013;Yan et al, 2013;Abrate et al, 2014;Altaner et al, 2014;Hu et al, 2014;Harati et al, 2015;Krasikova et al, 2015, Krassikova et al, 2016Lakota et al, 2015;Matuskova et al, 2015;Nouri et al, 2015;Chung et al, 2016;Yan et al, 2017;Yao et al, 2017;Mirzaei et al, 2018;Schug et al, 2018;Segaliny et al, 2019;Suryaprakash et al, 2019). In other studies, tumor cells and engineered MSCs were injected simultaneously in animal models (Fritz et al, 2008;Sasportas et al, 2009;You et al, 2009;Cavarretta et al, 2010;Seo et al, 2011;Altanerova et al, 2012;Fei et al, 2012;Zolochevska et al, 2012;Ahn et al, 2013;Kucerova et al, 2014;…”

Section: Resultsmentioning

confidence: 99%

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Pawitan

Bui

Mubarok

et al. 2020

Front. Cell Dev. Biol.

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Background: The therapeutic capacity of mesenchymal stem cells (also known as mesenchymal stromal cells/MSCs) depends on their ability to respond to the need of the damaged tissue by secreting beneficial paracrine factors. MSCs can be genetically engineered to express certain beneficial factors. The aim of this systematic review is to compile and analyze published scientific literatures that report the use of engineered MSCs for the treatment of various diseases/conditions, to discuss the mechanisms of action, and to assess the efficacy of engineered MSC treatment. Methods:We retrieved all published studies in PubMed/MEDLINE and Cochrane Library on July 27, 2019, without time restriction using the following keywords: "engineered MSC" and "therapy" or "manipulated MSC" and "therapy." In addition, relevant articles that were found during full text search were added. We identified 85 articles that were reviewed in this paper.Results: Of the 85 articles reviewed, 51 studies reported the use of engineered MSCs to treat tumor/cancer/malignancy/metastasis, whereas the other 34 studies tested engineered MSCs in treating non-tumor conditions. Most of the studies reported the use of MSCs in animal models, with only one study reporting a trial in human subjects. Thirty nine studies showed that the expression of beneficial paracrine factors would significantly enhance the therapeutic effects of the MSCs, whereas thirty three studies showed moderate effects, and one study in humans reported no effect. The mechanisms of action for MSC-based cancer treatment include the expression of "suicide genes," induction of tumor cell apoptosis, and delivery of cytokines to induce an immune response against cancer cells. In the context of the treatment of non-cancerous

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Mesenchymal stem cells: A new platform for targeting suicide genes in cancer

Tehrani

Verdi

Noureddini

et al. 2017

Journal Cellular Physiology

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One of the important strategies for the treatment of cancer is gene therapy which has the potential to exclusively eradicate malignant cells, without any damage to the normal tissues. Gene-directed enzyme prodrug therapy (GDEPT) is a two-step gene therapy approach, where a suicide gene is directed to tumor cells. The gene encodes an enzyme that expressed intracellularly where it is able to convert a prodrug into cytotoxic metabolites. Various delivery systems have been developed to achieve the appropriate levels of tumor restricted expression of chemotherapeutic drugs. Nowadays, mesenchymal stem cells (MSCs) have been drawing great attention as cellular vehicles for gene delivery systems. Inherent characteristics of MSCs make them particularly attractive gene therapy tools in cell therapy. They have been used largely for their remarkable homing property toward tumor sites and availability from many different adult tissues and show anti-inflammatory actions in some cases. They do not stimulate proliferative responses of lymphocytes, suggests that MSCs have low immunogenicity and could avoid immune rejection. This review summarizes the current state of knowledge about genetically modified MSCs that enable to co-transduce a variety of therapeutic agents including suicide genes (i.e., cytosine deaminase, thymidine kinase) in order to exert potent anti-carcinogenesis against various tumors growth. Moreover, we highlighted the role of exosomes released from MSCs as new therapeutic platform for targeting various therapeutic agents.

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Combined treatment, based on lysomustine administration with mesenchymal stem cells expressing cytosine deaminase therapy, leads to pronounced murine Lewis lung carcinoma growth inhibition

Cited by 9 publications

References 41 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

Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review

Mesenchymal stem cells: A new platform for targeting suicide genes in cancer

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