Antitumor activity of placenta-derived mesenchymal stem cells producing pigment epithelium-derived factor in a mouse melanoma model

Chen, Qiaoling; Cheng, Ping; Song, Na; Yin, Tao; He, Hong; Yang, Li; Chen, Xiancheng; Wei, Yuquan

doi:10.3892/ol.2012.772

Cited by 30 publications

(16 citation statements)

References 30 publications

(33 reference statements)

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“…In a study conducted by Chen et al, hMSCs derived from placenta were transfected with recombinant adenoviruses expressing pigment epithelium-derived factor (PEDF), and these hMSCs were able to inhibit melanoma cell growth. This anticancer activity was discussed to be the result of PEDF expression (40). Li et al demonstrated inhibition of gastric cancer cells by hMSCs derived from human foreskin (41).…”

Section: Discussionmentioning

confidence: 99%

The differentiation of hMSCs counteracts their migration capability and pro-angiogenic effects in vitro

et al. 2015

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Human mesenchymal stem cells (hMSCs) have been applied therapeutically in numerous clinical trials. The pro-angiogenic effects of hMSCs, as well as their strong tumor tropism, have been shown both in vitro and in vivo. Some studies suggest using hMSCs as potential drug-carriers for tumor therapy. In previous investigations by our group, the pro-tumorigenic effects of hMSCs on head and neck squamous cell carcinoma (HNSCC) were shown. However, the influence of hMSCs on tumor vascularization as well as the possibility of its inhibition are yet to be elucidated. The cytokine patterns of the HNSCC cell line FaDu, native hMSCs (hMSCs-nat), hMSCs differentiated into adipocytes (hMSCs-adip) and osteocytes (hMSCs-ost) were evaluated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with FaDu cells, hMSCs-nat, hMSCs-adip and hMSCs-ost. The capillary tube formation assay was applied. Furthermore, the migration capability of hMSCs-nat, hMSCs-adip and hMSCs-ost towards FaDu cells was measured in a Transwell system. Spheroids were cultured from hMSCs-nat, FaDu cells and DiI-labeled HUVECs. FaDu cells, hMSCs-nat, hMSCs-adip and hMSCs-ost released a wide range of cytokines and growth factors, e.g., IL-6, IL-8, IL-10, GRO and MCP. In the capillary tube formation assay, HUVECs generated significantly longer tubes after co-cultivation with hMSCs-nat as compared to HUVECs alone and FaDu. Differentiation into adipocytes and osteocytes counteracted the tube formation. The adipogenic differentiation did not alter hMSC motility, whereas osteogenic differentiation significantly inhibited hMSC migration. Generation of multi-cellular spheroids from hMSCs-nat, FaDu cells and DiI-labeled HUVECs was possible. Florescence microscopy revealed that all HUVECs were present in the spheroid core. Taken together, hMSCs-nat have a pro-angiogenic effect. The effects are counteracted by the differentiation of hMSCs towards osteogenic and adipogenic lineages. The differentiation of stem cells into different lineages may be a promising solution to generating carriers for cancer therapy without pro-tumorigenic properties.

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Section: Discussionmentioning

confidence: 99%

The differentiation of hMSCs counteracts their migration capability and pro-angiogenic effects in vitro

et al. 2015

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“…PEDF gene therapy might be a more promising therapeutic strategy in contrast to PEDF itself owing to more lasting curative effect, easier scale-up production and lower cost. PEDF gene indeed had better therapeutic efficacy on many tumors such as melanoma, hepatocellular carcinoma and colon carcinoma141516. Nevertheless, there was still no report about PEDF gene therapy for cervix cancer, probably lacking a specific and efficient delivery carrier.…”

mentioning

confidence: 99%

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

Yang

Liu

et al. 2016

Sci Rep

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Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.

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“…Therefore, they can be used as a coadjuvant for the expansion of CD34 + cells [Zhang et al, 2004;Parolini et al, 2008] and have been tested for multiple applications, including neuroprotection in hypoxic-ischemic brain damage in a murine model [Ding et al, 2015], as a gene delivery vehicle [Chen et al, 2012] and for myocardial therapy [Makhoul et al, 2013]. Similar to bone marrow mesenchymal stem cells, placenta-derived stem cells inhibit Tcell proliferation and secretion of IFN-γ; the immunosuppressive activity of placenta-derived stem cells against T cells involves PD-L1 (programmed death-ligand 1, also known as CD274) [Luan et al, 2013;Tripathi and Guleria, 2015].…”

Section: Placental Stem Cellsmentioning

confidence: 99%

The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix: A Review

Lobo¹,

Leonel²,

Miranda³

et al. 2016

Cells Tissues Organs

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The placenta is a temporal, dynamic and diverse organ with important immunological features that facilitate embryonic and fetal development and survival, notwithstanding the fact that several aspects of its formation and function closely resemble tumor progression. Placentation in mammals is commonly used to characterize the evolution of species, including insights into human evolution. Although most placentas are discarded after birth, they are a high-yield source for the isolation of stem/progenitor cells and are rich in extracellular matrix (ECM), representing an important resource for regenerative medicine purposes. Interactions among cells, ECM and bioactive molecules regulate tissue and organ generation and comprise the foundation of tissue engineering. In the present article, differences among several mammalian species regarding the placental types and classifications, phenotypes and potency of placenta-derived stem/progenitor cells, placental ECM components and current placental ECM applications were reviewed to highlight their potential clinical and biomedical relevance.

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Antitumor activity of placenta-derived mesenchymal stem cells producing pigment epithelium-derived factor in a mouse melanoma model

Cited by 30 publications

References 30 publications

The differentiation of hMSCs counteracts their migration capability and pro-angiogenic effects in vitro

The differentiation of hMSCs counteracts their migration capability and pro-angiogenic effects in vitro

Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα

The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix: A Review

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