Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues

Amano, Shinji; Li, Zhuoshi; Koizumi, Shinichiro; Tokuyama, Tsutomu; Namba, Hiroki

doi:10.1016/j.canlet.2011.02.037

Cited by 29 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These properties make MSCs a good candidate to carry HSV-Tk and to kill GBM. Importantly, the tumoricidal bystander effect of the MSCs modified with HSV-Tk does not harm normal brain tissues surrounding the tumor [36]. …”

Section: Introductionmentioning

confidence: 99%

The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

et al. 2015

View full text Add to dashboard Cite

Glioblastoma (GBM) is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs) that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs) were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues.

show abstract

Section: Introductionmentioning

confidence: 99%

The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In vivo preclinical studies confirming the feasibility of this approach for the treatment of glioma have been conducted using NSCs (17,44,83) and MSCs (81,(84)(85)(86)(87)(88)(89)(90) as HSV-tk delivery vehicles. It has also been proven that the 'bystander effect' of HSV-tk/GCV suicide gene therapy does not damage normal brain tissues (91).…”

Section: Enzyme/prodrug-based Therapy ('Suicide' Gene Therapy)mentioning

confidence: 99%

Use of genetically engineered stem cells for glioma therapy

2015

Self Cite

View full text Add to dashboard Cite

Abstract. Glioblastoma, the most common and most malignant type of primary brain tumor, is associated with poor prognosis, even when treated using combined therapies, including surgery followed by concomitant radiotherapy with temozolomide-based chemotherapy. The invasive nature of this type of tumor is a major reason underlying treatment failure. The tumor-tropic ability of neural and mesenchymal stem cells offers an alternative therapeutic approach, where these cells may be used as vehicles for the invasion of tumors. Stem cell-based therapy is particularly attractive due to its tumor selectivity, meaning that the stem cells are able to target tumor cells without harming healthy brain tissue, as well as the extensive tumor tropism of stem cells when delivering anti-tumor substances, even to distant tumor microsatellites. Stem cells have previously been used to deliver cytokine genes, suicide genes and oncolytic viruses. The present review will summarize current trends in experimental studies of stem cell-based gene therapy against gliomas, and discuss the potential concerns for translating these promising strategies into clinical use.

show abstract

“…Cellular vehicles, that have been proposed as transport systems, are summarized as follows: a) bone marrow stromal cells (MSCs) which exhibit the ability of homing to the tumor sites [39,68], b) neural stem cells (NSCs) which have an inherent tumor tropism [38,37], c) endothelial progenitor precursor and d) blood outgrowth endothelial cells. The last two target the vascular tumor tissue and are under investigation for clinical applications [43,44].…”

Section: Basic Strategies To Induce Cancer Cell Suicidementioning

confidence: 99%

“…In other studies, the stem cells were used as carrier of the transgenes. Moreover, the safety of MSCtk stem cell suicide gene therapy was investigated by Amano S. et al in a C6 glioma cell mouse model [68]. The study was performed to evaluate the safety of this treatment modality by intracranial and intraperitoneal administration.…”

Section: Suicide Gene Therapy Delivered With the Aid Of Stem Cellsmentioning

confidence: 99%

Suicide Gene Therapy for Cancer; Old Dog New Tricks

Zarogoulidis

Darwiche

Sakkas³

et al. 2013

J Genet Syndr Gene Ther

View full text Add to dashboard Cite

Current cancer treatments may create profound iatrogenic outcomes. The adverse effects of these treatments still remain, as the serious problems that practicing physicians have to cope with in clinical practice. Although, non-specific cytotoxic agents constitute an effective treatment modality against cancer cells, they also tend to kill normal, quickly dividing cells. On the other hand, therapies targeting the genome of the tumors are both under investigation, and some others are already streamlined to clinical practice. Several approaches have been investigated in order to find a treatment targeting the cancer cells, while not affecting the normal cells. Suicide gene therapy is a therapeutic strategy, in which cell suicide inducing transgenes are introduced into cancer cells. The two major suicide gene therapeutic strategies currently pursued are: cytosine deaminase/5-fluorocytosine and the herpes simplex virus/ganciclovir. The novel strategies include silencing gene expression, expression of intracellular antibodies blocking cells’ vital pathways, and transgenic expression of caspases and DNases. We analyze various elements of cancer cells’ suicide inducing strategies including: targets, vectors, and mechanisms. These strategies have been extensively investigated in various types of cancers, while exploring multiple delivery routes including viruses, non-viral vectors, liposomes, nanoparticles, and stem cells. We discuss various stages of streamlining of the suicide gene therapy into clinical oncology as applied to different types of cancer. Moreover, suicide gene therapy is in the center of attention as a strategy preventing cancer from developing in patients participating in the clinical trials of regenerative medicine. In oncology, these clinical trials are aimed at regenerating, with the aid of stem cells, of the patients’ organs damaged by pathologic and/or iatrogenic factors. However, the stem cells carry the risk of neoplasmic transformation. We discuss cell suicide inducing strategies aimed at preventing stem cell-originated cancerogenesis.

show abstract

Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues

Cited by 29 publications

References 35 publications

The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor

Use of genetically engineered stem cells for glioma therapy

Suicide Gene Therapy for Cancer; Old Dog New Tricks

Contact Info

Product

Resources

About