IFN-γ-primed human bone marrow mesenchymal stem cells induce tumor cell apoptosis in vitro via tumor necrosis factor-related apoptosis-inducing ligand

Du, Jingchun; Zhou, Liwen; Chen, Xiaoyong; Yan, Sunxing; Ke, Ming; Lu, Xiufen; Wang, Zhen; Yu, Weihua; Xiang, Andy Peng

doi:10.1016/j.biocel.2012.04.015

Cited by 37 publications

(41 citation statements)

References 43 publications

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“…After injection into nude mice along with H460 tumor cells, IFN- γ -modified MSCs still maintained an antiproliferative effect. The antitumor effect of IFN- γ -modified MSCs is obviously enhanced compared with that of IFN- γ -primed MSCs, as previously reported [12]. However, similar to our report, this study showed that tumor growth in mice injected with H460 cells was more prominent when MSCs were included [12].…”

Section: Discussionsupporting

confidence: 90%

“…The antitumor effect of IFN- γ -modified MSCs is obviously enhanced compared with that of IFN- γ -primed MSCs, as previously reported [12]. However, similar to our report, this study showed that tumor growth in mice injected with H460 cells was more prominent when MSCs were included [12]. A possible reason for this phenomenon may be that the proapoptotic capacity of IFN- γ -modified MSCs is dominant over the tumor-supportive capacity of unmodified MSCs, resulting in the inhibition of tumors by IFN- γ -modified MSCs.…”

Section: Discussionsupporting

confidence: 81%

“…Our previous report showed that IFN- γ induces MSCs to express TRAIL, which selectively mediates the apoptosis of tumor cells in vitro . However, the in vivo effect of IFN- γ -primed MSCs on tumor growth is different than that observed in vitro [12]. A primary reason for this discrepancy may be that the MSCs stimulated only once with IFN- γ could not maintain TRAIL expression, weakening the cytotoxic effect of the IFN- γ -primed MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…MSCs were isolated and cultured as previously described [12]. Briefly, BM aspirates were diluted with an equal volume of low-glucose, complete DMEM and then fractionated with Lymphoprep solution (Huajin, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

“…The current evidence suggests that the role of MSCs in tumor survival and progression is complex and diverse [11]. In our previous report, IFN- γ -primed MSCs were shown to express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which causes apoptosis in tumor cells [12]. However, the expression of TRAIL only persisted for approximately seventy-two hours after one priming with IFN- γ .…”

Section: Introductionmentioning

confidence: 99%

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IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor EffectIn Vivovia the TRAIL Pathway

Yang

et al. 2014

Journal of Immunology Research

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Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN-γ would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN-γ gene under the control of the EF1α promoter. The IFN-γ-modified MSCs effectively secreted functional IFN-γ, which led to long-term expression of TRAIL. More importantly, the IFN-γ-modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN-γ-modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN-γ-modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN-γ-modified MSCs.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor EffectIn Vivovia the TRAIL Pathway

Yang

et al. 2014

Journal of Immunology Research

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TRAIL is Involved in the Tumoricidal Activity of Mouse Natural Killer Cells Stimulated by Newcastle Disease Virus in Vitro

Song

Liang

Xiao

et al. 2013

The Anatomical Record

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Newcastle disease virus (NDV) is a potential antitumor agent, and its antitumor effect has been evaluated in preclinical tests. However, the mechanisms of NDV-based antitumor therapy are still not completely clear. In the present study we found that NDV-stimulation enhanced the killing ability of mouse spleen natural killer (NK) cells towards mouse hepatoma cell lines, and tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL) plays an important role in this tumoricidal activity. NDV stimulation induced up-regulation of TRAIL both at the mRNA and protein levels in NK cells. Blocking TRAIL by antibody (Ab) almost completely eliminated the killing effect of NK cells on hepatoma cell lines.

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The vascular nature of lung-resident mesenchymal stem cells

Steens

Klar

Hansel

et al. 2020

Stem Cells Translational Medicine

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Human lungs bear their own reservoir of endogenous mesenchymal stem cells (MSCs). Although described as located perivascular, the cellular identity of primary lung MSCs remains elusive. Here we investigated the vascular nature of lung-resident MSCs (LR-MSCs) using healthy human lung tissue. LR-MSCs predominately reside within the vascular stem cell niche, the so-called vasculogenic zone of adult lung arteries. Primary LR-MSCs isolated from normal human lung tissue showed typical MSC characteristics in vitro and were phenotypically and functionally indistinguishable from MSCs derived from the vascular wall of adult human blood vessels (VW-MSCs). Moreover, LR-MSCs expressed the VW-MSC-specific HOX code a characteristic to discriminate VW-MSCs from phenotypical similar cells. Thus, LR-MSC should be considered as VW-MSCs. Immunofluorescent analyses of non-small lung cancer (NSCLC) specimen further confirmed the vascular adventitia as stem cell niche for LR-MSCs, and revealed their mobilization and activation in NSCLC progression. These findings have implications for understanding the role of MSC in normal lung physiology and pulmonary diseases, as well as for the rational design of additional therapeutic approaches.

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IFN-γ-primed human bone marrow mesenchymal stem cells induce tumor cell apoptosis in vitro via tumor necrosis factor-related apoptosis-inducing ligand

Cited by 37 publications

References 43 publications

IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor EffectIn Vivovia the TRAIL Pathway

IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor EffectIn Vivovia the TRAIL Pathway

TRAIL is Involved in the Tumoricidal Activity of Mouse Natural Killer Cells Stimulated by Newcastle Disease Virus in Vitro

The vascular nature of lung-resident mesenchymal stem cells

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