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Extracellular Vesicle Derived From Mesenchymal Stem Cells Have Bidirectional Effects on the Development of Lung Cancer.

ABSTRACT: Mesenchymal stem cell is a kind of pluripotent cells with the ability of self-renewal and multi-directional differentiation, which exist in bone marrow, umbilical cord blood, umbilical cord tissue, placenta tissue, adipose tissue and so on. Extracellular vesicles are membranous lipid vesicles secreted by a variety of cells and widely present in body fluids, which contain proteins, mRNA, microRNA and other substances, and are an important medium of intercellular communication. At present, more and more evidence shows that mesenchymal stem cell-derived extracellular vesicles play an important role in the development of lung cancer. Regulating the levels of proteins, RNAs and other substances in MSC-EVs and then transplanting them into patients may be a new way to alleviate the development of lung cancer. We mainly introduce the role of extracellular vesicles derived from human umbilical cord mesenchymal stem cells, bone marrow mesenchymal stem cells and adipose mesenchymal stem cells in lung cancer, to provide new alternatives for the treatment of lung cancer.

SUBMITTER: Wang J

PROVIDER: S-EPMC9289533 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Extracellular Vesicle Derived From Mesenchymal Stem Cells Have Bidirectional Effects on the Development of Lung Cancer.

Wang Jiayu J Ma Yiming Y Long Yingjiao Y Chen Yan Y

Frontiers in oncology 20220704

Mesenchymal stem cell is a kind of pluripotent cells with the ability of self-renewal and multi-directional differentiation, which exist in bone marrow, umbilical cord blood, umbilical cord tissue, placenta tissue, adipose tissue and so on. Extracellular vesicles are membranous lipid vesicles secreted by a variety of cells and widely present in body fluids, which contain proteins, mRNA, microRNA and other substances, and are an important medium of intercellular communication. At present, more an ...[more]

PMID: 35860555

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Project description:BackgroundExtracellular vesicles (EVs) and their mimics from mesenchymal stem cells (MSCs) are promising drug carriers to improve cancer treatment, but their application is hindered by donor variations and expansion limitations of conventional tissue-derived MSCs. To circumvent these issues, we made EV-mimicking nanovesicles from standardized MSCs derived from human induced pluripotent stem cells (iPSCs) with a theoretically limitless expandability, and examined the targeting capacity of these nanovesicles to prostate cancer.MethodsNanovesicles are made from intact iPSC-MSCs through serial extrusion. The selective uptake of fluorescently labeled nanovesicles by prostate cancer cells vs. non-tumor cells was examined with flow cytometry. For in vivo tracing, nanovesicles were labeled with fluorescent dye DiR or renilla luciferase. In mice carrying subcutaneous or bone metastatic PC3 prostate cancer, the biodistribution of systemically infused nanovesicles was examined with in vivo and ex vivo imaging of DiR and luminescent signals. A chemotherapeutic drug, docetaxel, was loaded into nanovesicles during extrusion. The cytotoxicities of nanovesicle-encapsulated docetaxel on docetaxel-sensitive and -resistant prostate cancer cells and non-tumor cells were examined in comparison with free docetaxel. Therapeutic effects of nanovesicle-encapsulated docetaxel were examined in mice carrying subcutaneous or bone metastatic prostate cancer by monitoring tumor growth in comparison with free docetaxel.ResultsiPSC-MSC nanovesicles are more selectively taken up by prostate cancer cells vs. non-tumor cells in vitro compared with EVs, membrane-only EV-mimetic nanoghosts and liposomes, which is not affected by storage for up to 6 weeks. In mouse models of subcutaneous and bone metastatic PC3 prostate cancer, systemically infused nanovesicles accumulate in tumor regions with significantly higher selectivity than liposomes. The loading of docetaxel into nanovesicles was efficient and did not affect the selective uptake of nanovesicles by prostate cancer cells. The cytotoxicities of nanovesicle-encapsulated docetaxel are significantly stronger on docetaxel-resistant prostate cancer cells and weaker on non-tumor cells than free docetaxel. In mouse models of subcutaneous and bone metastatic prostate cancer, nanovesicle-encapsulated docetaxel significantly decreased the tumor growth and toxicity to white blood cells compared with free docetaxel.ConclusionsOur data indicate that EV-mimicking iPSC-MSC nanovesicles are promising to improve the treatment of metastatic prostate cancer.

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Extracellular Vesicle Derived From Mesenchymal Stem Cells Have Bidirectional Effects on the Development of Lung Cancer.

Publications

Extracellular Vesicle Derived From Mesenchymal Stem Cells Have Bidirectional Effects on the Development of Lung Cancer.

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