Genetically engineered mesenchymal stromal cells producing TNFα have tumour suppressing effect on human melanoma xenograft

Tyciakova, Silvia; Matúšková, Miroslava; Bohovic, Roman; Poláková, K; Toro, Lenka; Skolekova, Svetlana; Kučerová, Lucia

doi:10.1002/jgm.2823

Cited by 36 publications

(29 citation statements)

References 46 publications

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“…Some studies have shown that MSCs suppress tumor progression by inducing apoptosis or arresting cell cycle [18,32,33], whereas others have shown that hMSCs promote tumor progression by suppressing immune responses [34e36], promoting angiogenesis [37e41] and promoting cancer cell proliferation [42e44]. However, it is notable that the studies that showed anti-cancer effects of MSC or MSC with TNF-a used TRAIL-sensitive cancer cell lines, such as A375, SJBR3 and MDA-MB-231.…”

Section: Discussionmentioning

confidence: 99%

Pre-activated human mesenchymal stromal cells in combination with doxorubicin synergistically enhance tumor-suppressive activity in mice

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Pre-activated human mesenchymal stromal cells in combination with doxorubicin synergistically enhance tumor-suppressive activity in mice

et al. 2015

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“…Tumor tropism of MSCs has been exploited for the delivery of therapeutic genes in anticancer therapy, and this approach has proven to be successful in different preclinical models of cancer . However, for clinical use, it would be desirable if localization of sufficient MSCs within tumors could be achieved by MSC‐mediated gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Chemokine CCL15 Mediates Migration of Human Bone Marrow-Derived Mesenchymal Stem Cells Toward Hepatocellular Carcinoma

Gao

Zhou

et al. 2016

Stem Cells

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Mesenchymal stem cells (MSCs) possess the ability to migrate toward tumor sites and are regarded as promising gene delivery vehicles for cancer therapeutics. However, the factors that mediate this tropism have yet to be completely elucidated. In this study, through cytokine array analysis, chemokine CCL15 was found to be the most abundant protein differentially expressed in hepatocellular carcinoma (HCC) cell lines compared with a normal liver cell line. Serum CCL15 levels in HCC patients determined by enzyme linked immunosorbent assay were shown to be profoundly elevated compared with healthy controls. Immunohistochemical analysis indicated that CCL15 expression was much stronger in HCC tumor tissues than in adjacent nontumor tissues. Transwell migration assay suggested that CCL15 may be involved in chemotaxis of human MSCs (hMSCs) toward HCC in vitro and that this chemotactic effect of CCL15 is mediated via CCR1 receptors on hMSCs. Orthotopic animal models of HCC were established to investigate the role of CCL15 in hMSCs migration toward HCC in vivo. Both histological and flow cytometric analysis showed that significantly fewer hMSCs localized within 97H-CCL15-shRNA xenografts compared with 97H-green fluorescent protein xenografts after intravenous delivery. Finally, the possible effects of hMSCs on HCC tumor growth were also evaluated. Coculture experiments showed that hMSCs had no apparent effect on the proliferation of HCC cells in vitro In addition, systemic administration of hMSCs did not affect HCC tumor progression in vivo. Our data in this study help to elucidate the mechanism underlying the homing capacity of hMSCs toward HCC. STEM CELLS 2016;34:1112-1122 SIGNIFICANCE STATEMENTMesenchymal stem cells (MSCs) possess the ability to migrate toward tumor sites and are regarded as promising gene delivery vehicles for cancer therapeutics. In this study, HCC-derived CCL15 was demonstrated to be a chemoattractant for MSCs both in vitro and in vivo, and that this tropism of hMSCs for HCC is mainly mediated through the CCL15/CCR1 axis. Our data in the present study help to elucidate the mechanism underlying the homing capacity of hMSCs toward HCC and may be exploited to improve the therapeutic efficacy of hMSCs in the treatment of HCC.

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“…To further reinforce the potency of MSCs, they can be expanded and genetically manipulated under standard cell culture conditions, making them an attractive target for cellular gene therapy . Various gene delivery vectors for MSCs, including nonviral systems based on eukaryotic expression plasmids, transposons and artificial chromosomes, as well as viral vectors derived from retro‐, lenti‐, adeno‐, baculo‐ and adeno‐associated viruses, are currently available . Each transfer vector has specific benefits and disadvantages, which have to be carefully evaluated with regard to its particular final application.…”

Section: Introductionmentioning

confidence: 99%

Inflammation‐induced transgene expression in genetically engineered equine mesenchymal stem cells

Gabner

Hlavatý

Velde

et al. 2016

The Journal of Gene Medicine

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Genetically engineered mesenchymal stromal cells producing TNFα have tumour suppressing effect on human melanoma xenograft

Abstract: The results of the present study demonstrate that tumour cells respond to hTNFα-based treatment mediated by genetically engineered AT-MSC/hTNFα both in vitro and in vivo.

Cited by 36 publications

References 46 publications

Pre-activated human mesenchymal stromal cells in combination with doxorubicin synergistically enhance tumor-suppressive activity in mice

Pre-activated human mesenchymal stromal cells in combination with doxorubicin synergistically enhance tumor-suppressive activity in mice

Chemokine CCL15 Mediates Migration of Human Bone Marrow-Derived Mesenchymal Stem Cells Toward Hepatocellular Carcinoma

Inflammation‐induced transgene expression in genetically engineered equine mesenchymal stem cells

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