Human glioma stem-like cells induce malignant transformation of bone marrow mesenchymal stem cells by activating TERT expression

Zhao, Yuhai; Chen, Jinsheng; Cai, Heng; Ji, Xiaoyan; Sheng, Yujing; Liu, Hairui; Yang, Lin; Chen, Yanming; Xi, Dengguo; Sheng, Minfeng; Xue, Yadong; Shi, Jia; Liu, Jiachi; Li, Xiaonan; Dong, Jun

doi:10.18632/oncotarget.22301

Cited by 9 publications

(6 citation statements)

References 33 publications

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“…The cells were stained with Alizarin Red S to detect calcium deposition ( 23 ). The BMSCs were washed three times with PBS and then fixed with 70% ethanol for 1 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Role of TGF‑β1 expressed in bone marrow‑derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model

et al. 2018

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Bone defects represent a major clinical and socioeconomic problem without suitable treatment options. Previous studies have shown that transforming growth factor β1 (TGF-β1) is important in the development of various diseases. The present study aimed to investigate the therapeutic potential of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) expressing TGF-β1 in the treatment of rabbit femoral defects. First, rabbit BMSCs were identified and cultured. TGF-β1 was then stably overexpressed in the rabbit BMSCs by lentivirus transfection, which was expressed at a high level in the femoral defects treated with TGF-β1-overexpressing BMSCs, compared with PBS-treated controls. In addition, the TGF-β1-overexpressing BMSCs promoted new bone formation in the rabbit femoral defect model, and increased the expression of bone-related markers at week 2 and week 6. Therefore, the study demonstrated that BMSCs overexpressing TGF-β1 may provide a novel therapeutic option for femoral defects.

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“…The cells were stained with Alizarin Red S to detect calcium deposition ( 23 ). The BMSCs were washed three times with PBS and then fixed with 70% ethanol for 1 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Role of TGF‑β1 expressed in bone marrow‑derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model

et al. 2018

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“…Studies have shown that BMSCs have a similar self-renewal ability as cancer cells, and possess the ability to transform spontaneously in vitro. It has also been suggested that tumors may transform from highly invasive mesenchymal stem cells [ 37 ], especially in the tumor microenvironment [ 38 ]. In addition, Japanese scientists confirmed that there was still a significant difference in the expression of proliferating genes between BMSCs and cancer cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model

Xie

et al. 2021

J Transl Med

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Background Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice Methods The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured Results There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) Conclusions This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.

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“…Glioma stem cells (GSCs) are also able to induce malignant transformation of BMSCs by activating TERT expression. Besides, transformed BMSCs are able to generate subcutaneous tumors when transplanted in athymic nude mice [55]. In addition, C6 glioma-conditioned medium (GCM) induces malignant transformation of MSCs.…”

Section: Discussionmentioning

confidence: 99%

Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival

Iser

Beckenkamp

Azambuja

et al. 2021

Stem Cell Rev and Rep

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Many studies have shown that mesenchymal stromal cells (MSCs) and their secreted factors may modulate the biology of tumor cells. However, how these interactions happen in vivo remains unclear. In the present study, we investigated the effects of rat adipose-derived stromal cells (ADSCs) and their conditioned medium (ADSC-CM) in glioma tumor growth and malignancy in vivo. Our results showed that when we co-injected C6 cells plus ADSCs into the rat brains, the tumors generated were larger and the animals exhibited shorter survival, when compared with tumors of the animals that received only C6 cells or C6 cells pre-treated with ADSC-CM. We further showed that the animals that received C6 plus ADSC did not present enhanced expression of CD73 (a gene highly expressed in ADSCs), indicating that the tumor volume observed in these animals was not a mere consequence of the higher density of cells administered in this group. Finally, we showed that the animals that received C6 + ADSC presented tumors with larger necrosis areas and greater infiltration of immune cells. These results indicate that the immunoregulatory properties of ADSCs and its contribution to tumor stroma can support tumor growth leading to larger zones of necrosis, recruitment of immune cells, thus facilitating tumor progression. Our data provide new insights into the way by which ADSCs and tumor cells interact and highlight the importance of understanding the fate and roles of MSCs in tumor sites in vivo, as well as their intricate crosstalk with cancer cells. KeywordsRat adipose-derived stromal cell (ADSC) • Conditioned medium • C6 glioma cell • Tumor microenvironment • Astrocytes • Orthotopic glioma model in rat * Márcia Rosângela Wink Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Human glioma stem-like cells induce malignant transformation of bone marrow mesenchymal stem cells by activating TERT expression

Cited by 9 publications

References 33 publications

Role of TGF‑β1 expressed in bone marrow‑derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model

Role of TGF‑β1 expressed in bone marrow‑derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model

Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model

Rat Adipose-Derived Stromal Cells (ADSCs) Increases the Glioblastoma Growth and Decreases the Animal Survival

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