Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas

Zhang, Qing; Xiang, Wei; Yi, Dong-Ye; Xue, Bing-Zhou; Wen, Wanwan; Abd‐Elmaksoud, Ahmed; Xiong, Nanxiang; Jiang, Xiaobing; Zhao, Hongyang; Fu, Peng

doi:10.1186/s13287-018-0977-z

Cited by 70 publications

(69 citation statements)

References 92 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In MSCs group, low hypercellularity and mitosis index as well as mild invasive of tumor cells without pseudopalisading necrosis indicate that the anticancer effect of MSCs in a rat model of GBM. It has been shown that by means of tumour-specific tropism of MSCs can be transduced to deliver anticancer agents such as interleukins (IL-2, IL-7, IL-18, and IL-12), TRAIL, and interferon (IFN-β and IFN-γ) directly to glioma sites to kill tumour cells or to regulate immune responses [ 2 , 4 , 35 , 36 ]. Mild or limited invasive tumoral cells associated with low microvascular proliferation without pseudopalisading necrosis, in Ator + MSCs group shows that simultaneous utilization of MSCs and Ator can exert more anticancer activity against GBM rather than MSCs and Ator alone in experimental GBM model.…”

Section: Resultsmentioning

confidence: 99%

Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

Goodarzi

Khanmohammadi

et al. 2020

Mol Biol Rep

View full text Add to dashboard Cite

Glioblastoma multiform (GBM) is known as an aggressive glial neoplasm. Recently incorporation of mesenchymal stem cells with anti-tumor drugs have been used due to lack of immunological responses and their easy accessibility. In this study, we have investigated the anti-proliferative and apoptotic activity of atorvastatin (Ator) in combination of mesenchymal stem cells (MSCs) on GBM cells in vitro and in vivo. The MSCs isolated from rats and characterized for their multi-potency features. The anti-proliferative and migration inhibition of Ator and MSCs were evaluated by MTT and scratch migration assays. The annexin/PI percentage and cell cycle arrest of treated C6 cells were evaluated until 72 h incubation. The animal model was established via injection of C6 cells in the brain of rats and subsequent injection of Ator each 3 days and single injection of MSCs until 12 days. The growth rate, migrational phenotype and cell cycle progression of C6 cells decreased and inhibited by the interplay of different factors in the presence of Ator and MSCs. The effect of Ator and MSCs on animal models displayed a significant reduction in tumor size and weight. Furthermore, histopathology evaluation proved low hypercellularity and mitosis index as well as mild invasive tumor cells for perivascular cuffing without pseudopalisading necrosis and small delicate vessels in Ator + MSCs condition. In summary, Ator and MSCs delivery to GBM model provides an effective strategy for targeted therapy of brain tumor.

show abstract

Section: Resultsmentioning

confidence: 99%

Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

Goodarzi

Khanmohammadi

et al. 2020

Mol Biol Rep

View full text Add to dashboard Cite

show abstract

“…We propose that use of MSCs as a carrier of IFNb may provide advantages over intratumoral gene therapy. In particular, the MSC approach is expected to be transient when applied in vivo, since cells may migrate out of the tumor, differentiate, or die (9,10). The adenovirus that they carry cannot replicate and is not integrated in the host genome, therefore this approach is incompatible with stable, long term exogenous gene expression (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…For the latter, autologous MSCs may be isolated from the circulation, bone marrow, or adipose tissue, including lipoaspirates, cultivated in the laboratory, modified and expanded ex vivo, and then infused in the patient (4)(5)(6). The use of MSCs as a delivery vehicle for the therapeutic payload has been shown to home to and infiltrate the tumor site where they provide therapeutic transgene levels while shielding the gene transfer vector from immune recognition (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

p19Arf sensitizes B16 melanoma cells to interferon-β delivered via mesenchymal stem cells in vitro

DaCosta

Vieira

Hunger

et al. 2020

Braz J Med Biol Res

View full text Add to dashboard Cite

The immune stimulatory and anti-neoplastic functions of type I interferon have long been applied for the treatment of melanoma. However, the systemic application of high levels of this recombinant protein is often met with toxicity. An approach that provides localized, yet transient, production of type I interferon may overcome this limitation. We propose that the use of mesenchymal stem cells (MSCs) as delivery vehicles for the production of interferon-b (IFNb) may be beneficial when applied together with our cancer gene therapy approach. In our previous studies, we have shown that adenovirus-mediated gene therapy with IFNb was especially effective in combination with p19Arf gene transfer, resulting in immunogenic cell death. Here we showed that MSCs derived from mouse adipose tissue were susceptible to transduction with adenovirus, expressed the transgene reliably, and yet were not especially sensitive to IFNb production. MSCs used to produce IFNb inhibited B16 mouse melanoma cells in a co-culture assay. Moreover, the presence of p19Arf in the B16 cells sensitizes them to the IFNb produced by the MSCs. These data represent a critical demonstration of the use of MSCs as carriers of adenovirus encoding IFNb and applied as an anticancer strategy in combination with p19Arf gene therapy.

show abstract

“…GBM expresses a variety of proteins that bind to T cell surface receptors, leading to T cell dysfunction and apoptosis [ 1 , 2 ], and GBM microenvironment signals, such as TGF-β and IL-10, induce local and systemic immunosuppression [ 3 ]. Despite the introduction of concomitant and adjuvant radiotherapy and chemotherapy, patient prognosis remains unsatisfactory, with an almost 15 months median survival [ 4 – 6 ]. These poor outcomes are partially linked to extreme degrees of genetic and phenotypic variation, as well as therapeutic resistance [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Zhang

Tian

et al. 2020

Cell Biosci

Self Cite

View full text Add to dashboard Cite

Background Glioblastoma (GBM) is an immunosuppressive, highly vascular and devastating malignant brain tumor. Even with progressive combination treatment that includes surgery, radiotherapy, and chemotherapy, the prognosis for GBM patients is still extremely poor. Oncolytic adenovirus (OAd) can specifically replicate in GBM cells, permitting the rapid copy of the therapeutic genes it carries. Moreover, E1A is an essential gene in adenoviral replication and is the first gene expressed upon viral infection. E1A expression can be regulated by the Ki67 promoter, while the CMV promoter drives therapeutic gene expression. However, the efficacy of a double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 against GBM cells has not been investigated. Methods Fluorescence microscopy was performed to evaluate infection ability in the viruses. Cell viability was detected by CCK-8 assay. Levels of cytokines in different supernatants were determined by ELISA, and IL-15 gene expression was measured by RT-PCR. Angiogenic capacity was analyzed by tube formation assay. Results We successfully constructed a double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 that selectively infected and killed GBM cells while sparing normal cells. The adenoviruses prime IL-15 gene expression to significantly enhance anti-GBM efficacy through effective activation of microglial cells. Moreover, OAd not only directly inhibits angiogenesis but exhibits potent antiangiogenic capacity mediated by the reduction of VEGF secretion. Conclusions These results provide new insight into the effects of a novel double-controlled OAd driven by the Ki67 core promoter and armed with IL-15 in glioblastoma treatment, which may help in the development of novel therapies in solid tumors.

show abstract

Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas

Cited by 70 publications

References 92 publications

Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

Simultaneous impact of atorvastatin and mesenchymal stem cells for glioblastoma multiform suppression in rat glioblastoma multiform model

p19Arf sensitizes B16 melanoma cells to interferon-β delivered via mesenchymal stem cells in vitro

Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells

Contact Info

Product

Resources

About