Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma

Khakoo, Aarif Y.; Pati, Shibani; Anderson, Stasia A.; Reid, William; Elshal, Mohamed F.; Rovira, Ilsa I.; Nguyen, Ahn; Malide, Daniela; Combs, Christian A.; Hall, Gentzon; Jian-hu, Zhang; Rogers, Terry B.; Stetler‐Stevenson, William G.; Frank, Joseph A.; Reitz, Marvin S.; Finkel, Toren

doi:10.1083/jcb1734oia7

Cited by 212 publications

(320 citation statements)

References 46 publications

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“…In the present direct co-culture studies, the majority of dead cells were observed around MSC occupied areas, consistent with our previous findings with liver cancer cells. 24 The innate antitumor effects of MSCs have been previously recognized in experimental Kaposi's sarcoma, 12 hepatocellular carcinoma, 36 and colorectal carcinoma 37 studies. The direct effects of MSCs on tumor cell viability are mainly attributed to their intrinsic antitumor properties.…”

Section: Dynamic Observation Of Msc Migration Toward Pancreatic Cancementioning

confidence: 98%

“…7 Tumor-directed migration and incorporation of MSCs have been demonstrated in a number of preclinical studies in vitro using transwell migration assays, and in vivo using animal tumor models. The homing capacity of MSCs has been demonstrated with almost all tested human cancer cell lines, including lung cancer, 8 malignant gliomas, 9--11 Kaposi's sarcomas, 12 breast cancer, 13,14 colon carcinoma, 15 pancreatic cancer, 16,17 melanoma 18 and ovarian cancer. 13 Engineered with tumor-specific anticancer genes, MSCs are capable of producing anticancer agents locally and constantly at the tumor site.…”

Section: Introductionmentioning

confidence: 99%

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TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

Sun

Rayat

et al. 2012

Cancer Gene Ther

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Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreasderived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSC nsTRAIL and MSC stTRAIL . The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.

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Section: Dynamic Observation Of Msc Migration Toward Pancreatic Cancementioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

Sun

Rayat

et al. 2012

Cancer Gene Ther

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“…These results indicated that MSCs selectively migrated to the tumor tissues of the lung, consistent with previous reports that the tumor microenvironment preferentially promotes the engraftment of MSCs. [7][8][9]23,24 Inhibition of C-26 lung metastases and survival prolongation by NK4-MSCs First, we determined the NK4 expression in the lungs with tumors. A significant amount of NK4 protein was detected after NK4-MSCs injection, although it was very much lower than that by direct instillation of Ad-RGDNK4 (Figure 4a).…”

Section: Construction Of Ad-rgdnk4 and Expression Of Nk4 Protein In Mscsmentioning

confidence: 99%

Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells

et al. 2007

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Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumorbearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.

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“…Mesenchymal stromal cells are useful in delivering therapeutic protein to specific tissues as they can migrate to tumor or injury sites (Khakoo et al 2006;Kidd et al 2010;Pittenger and Martin 2004;Tomita et al 2002;Yen and Yen 2008). This offers an alternative treatment in lieu of recombinant protein therapy, as it reduces the cost of treatment, development of auto-antibody, and risks related to high concentration of recombinant proteins in the blood stream (Bennett et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Extended and stable gene expression via nucleofection of MIDGE construct into adult human marrow mesenchymal stromal cells

et al. 2011

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Human mesenchymal stromal cell (hMSC) is a potential target for cell and gene therapy-based approaches against a variety of different diseases. Whilst cationic lipofection has been widely experimented, the Nucleofector technology is a relatively new non-viral transfection method designed for primary cells and hard-to-transfect cell lines. Herein, we compared the efficiency and viability of nucleofection with cationic lipofection, and used the more efficient transfection method, nucleofection, to deliver a construct of minimalistic, immunologically defined gene expression encoding the erythropoietin (MIDGE-EPO) into hMSC. MIDGE construct is relatively safer than the viral and plasmid expression systems as the detrimental eukaryotic and prokaryotic gene and sequences have been eliminated. Using a plasmid encoding the luciferase gene, we demonstrated a high transfection efficiency using the U-23 (21.79 ± 1.09%) and C-17 (5.62 ± 1.09%) pulsing program in nucleofection. The cell viabilities were (44.93 ± 10.10)% and (21.93 ± 5.72)%, respectively 24 h post-nucleofection. On the other hand, lipofection treatment only yielded less than 0.6% efficiencies despite showing higher viabilities. Nucleofection did not affect hMSC renewability, immunophenotype and differentiation potentials. Subsequently, we nucleofected MIDGE-EPO using the U-23 pulsing program into hMSC. The results showed that, despite a low nucleofection efficiency with this construct, the EPO protein was stably expressed in the nucleofected cells up to 55 days when determined by ELISA or immunocytochemical staining. In conclusion, nucleofection is an efficient non-viral transfection approach for hMSC, which when used in conjunction with a MIDGE construct, could result in extended and stable transgene expression in hMSC.

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Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma

Cited by 212 publications

References 46 publications

TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells

Extended and stable gene expression via nucleofection of MIDGE construct into adult human marrow mesenchymal stromal cells

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