TRAIL Based Therapy: Overview of Mesenchymal Stem Cell Based Delivery and miRNA Controlled Expression of TRAIL

Attar, Rukset; Sajjad, Farhana; Qureshi, Muhammad Zahid; Tahir, Fizza; Hussain, Ejaz; Fayyaz, Sundas; Farooqı, Ammad Ahmad

doi:10.7314/apjcp.2014.15.16.6495

Cited by 9 publications

(9 citation statements)

References 19 publications

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“…No path exists independently in cell reactions and each pathway may integrate with many other pathways. The intensity of the regulation and the interplay between signaling pathways decides the fate of the associated cells ( 1 ). The results of the present experiment indicate that the tumor microenvironment is able to induce spontaneous changes in the proliferation and migration ability of BM-MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Malignant tumors are a serious threat to human health and emphasis has been placed on developing novel therapies to treat such malignancies. Tumor biological therapy is the application of modern biological technology and products targeted at tumors to effectively ameliorate the side effects of chemotherapy ( 1 ). Bone marrow mesenchymal stem cells (BM-MSCs) cultured in vitro can be induced to proliferate, readily undergo transfection with liposomes carrying exogenous genes, have excellent mobility, are capable of undergoing multilineage differentiation ( 2 ) and have low immunogenicity ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

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Co-culture with lung cancer A549 cells promotes the proliferation and migration of mesenchymal stem cells derived from bone marrow

Zhang

Guan

et al. 2017

Experimental and Therapeutic Medicine

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The initiation and progression of various types of tumors, such as lung neoplasms, are driven by a population of cells with stem cell properties and their microenvironment. Bone marrow mesenchymal stem cells (BM-MSCs) in long-term in vitro culture may exhibit spontaneous changes in stem cell biological properties, including malignant transformations; however, the molecular mechanisms of this have not been fully elucidated. In the present study, a BM-MSC and lung cancer A549 cell co-culture system was utilized to investigate how the tumor microenvironment may spontaneously change the proliferation, migration and differentiation of BM-MSCs. It was demonstrated that the lung cancer A549 microenvironment is able to induce changes in the cell morphology, proliferation, karyotype, cytoskeleton and migration ability of BM-MSCs in vitro. Compared with the control group BM-MSCs, the expression of Ras, phosphorylated-extracellular regulated protein kinases, nuclear factor-κB, P62 and B-cell lymphoma 2 (Bcl-2) proteins in groups of co-cultured BM-MSCs increased significantly (P<0.05) and the expression of P53, Bcl-2 associated X protein and caspase-3 protein decreased significantly (P<0.05). The mechanisms responsible for the changes observed in BM-MSCs may be related to abnormal expression of related genes in the ERK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Co-culture with lung cancer A549 cells promotes the proliferation and migration of mesenchymal stem cells derived from bone marrow

Zhang

Guan

et al. 2017

Experimental and Therapeutic Medicine

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“…MSCs can also specifically migrate to a tumor site, as tumorigenesis is a chronic inflammatory process [6]. Thus, MSCs are commonly considered ideal antitumor vehicles to express anticancer agents or immune cytokines [7][8][9][10][11][12][13][14][15][16][17][18]. However, the mechanism underlying the effects of MSCs on tumor progression remains unclear and represents a potential problem for their clinical application.…”

Section: Introductionmentioning

confidence: 99%

Opposite Effects of Coinjection and Distant Injection of Mesenchymal Stem Cells on Breast Tumor Cell Growth

Zheng

Zou

Shen

et al. 2016

Stem Cells Translational Medicine

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Mesenchymal stem cells (MSCs) usually promote tumor growth and metastasis. By using a breast tumor 4T1 cell-based animal model, this study determined that coinjection and distant injection of allogeneic bone marrow-derived MSCs with tumor cells could exert different effects on tumor growth. Whereas the coinjection of MSCs with 4T1 cells promoted tumor growth, surprisingly, the injection of MSCs at a site distant from the 4T1 cell inoculation site suppressed tumor growth. We further observed that, in the distant injection model, MSCs decreased the accumulation of myeloid-derived suppressor cells and regulatory T cells in tumor tissues by enhancing proinflammatory factors such as interferon-g, tumor necrosis factor-a, Toll-like receptor (TLR)-3, and TLR-4, promoting host antitumor immunity and inhibiting tumor growth. Unlike previous reports, this is the first study reporting that MSCs may exert opposite roles on tumor growth in the same animal model by modulating the host immune system, which may shed light on the potential application of MSCs as vehicles for tumor therapy and other clinical applications. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1216-1228 SIGNIFICANCEMesenchymal stem cells (MSCs) have been widely investigated for their potential roles in tissue engineering, autoimmune diseases, and tumor therapeutics. This study explored the impact of coinjection and distant injection of allogeneic bone marrow-derived MSCs on mouse 4T1 breast cancer cells. The results showed that the coinjection of MSCs and 4T1 cells promoted tumor growth. MSCs might act as the tumor stromal precursors and cause immunosuppression to protect tumor cells from immunosurveillance, which subsequently facilitated tumor metastasis. Interestingly, the distant injection of MSCs and 4T1 cells suppressed tumor growth. Together, the results of this study revealed the dual functions of MSCs in immunoregulation.

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“…Moreover, MSCs exhibit an inherent ability to home towards tumors of various tissue origin including carcinomas of breast, lung, pancreas, and ovary. The tumor homing capacity was used to deliver therapeutic products to the tumor site by applying genetically engineered MSCs [11][12][13][14][15][16][17]. In particular, the capacity to actively migrate into the tumor tissue and the ease to engineer the cells by viral vectors makes MSCs attractive for delivering transgenic immune modulators in order to shift the tumor bed from an inhibitory to an immune stimulatory environment [18].…”

Section: Introductionmentioning

confidence: 99%

IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells

Hombach

Geumann

Günther

et al. 2020

Cells

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Chimeric antigen receptor (CAR) redirected T cells are efficacious in the treatment of leukemia/lymphoma, however, showed less capacities in eliminating solid tumors which is thought to be partly due to the lack of cytokine support in the tumor lesion. In order to deliver supportive cytokines, we took advantage of the inherent ability of mesenchymal stem cells (MSCs) to actively migrate to tumor sites and engineered MSCs to release both IL7 and IL12 to promote homeostatic expansion and Th1 polarization. There is a mutual interaction between engineered MSCs and CAR T cells; in presence of CAR T cell released IFN-γ and TNF-α, chronic inflammatory Th2 MSCs shifted towards a Th17/Th1 pattern with IL2 and IL15 release that mutually activated CAR T cells with extended persistence, amplification, killing and protection from activation induced cell death. MSCs releasing IL7 and IL12 were superior over non-modified MSCs in supporting the CAR T cell response and improved the anti-tumor attack in a transplant tumor model. Data demonstrate the first use of genetically modified MSCs as vehicles to deliver immuno-modulatory proteins to the tumor tissue in order to improve the efficacy of CAR T cells in the treatment of solid malignancies.

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TRAIL Based Therapy: Overview of Mesenchymal Stem Cell Based Delivery and miRNA Controlled Expression of TRAIL

Cited by 9 publications

References 19 publications

Co-culture with lung cancer A549 cells promotes the proliferation and migration of mesenchymal stem cells derived from bone marrow

Co-culture with lung cancer A549 cells promotes the proliferation and migration of mesenchymal stem cells derived from bone marrow

Opposite Effects of Coinjection and Distant Injection of Mesenchymal Stem Cells on Breast Tumor Cell Growth

IL7-IL12 Engineered Mesenchymal Stem Cells (MSCs) Improve A CAR T Cell Attack Against Colorectal Cancer Cells

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