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Exosomes: Insights and therapeutic applications in cancer.

ABSTRACT: Cancer refers to the division of abnormal cells at an uncontrollable rate that possesses the ability to infiltrate and destroy normal tissues. It frequently spreads to normal tissues throughout the body, a condition known as metastasis, which is a significant concern. It is the second leading cause of mortality globally and treatment therapy can assist in improving survival rates. Exosomes are the extracellular vesicles secreted by several cells that act as messengers between cells. When engineered, exosomes act as promising drug delivery vehicles that help achieve targeted action at the tumour site and reduce the limitations of conventional treatments such as castration, chemotherapy, radiation, etc. The present review provides an overview of exosomes, the biogenesis, sources, isolation methods and characterization. The current status and applications of chemotherapeutic agents loaded, engineered exosomes in cancer treatment were convoluted.

SUBMITTER: Panigrahi AR

PROVIDER: S-EPMC9108525 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Exosomes: Insights and therapeutic applications in cancer.

Panigrahi Anita Raj AR Srinivas Lankalapalli L Panda Jagadeesh J

Translational oncology 20220509

Cancer refers to the division of abnormal cells at an uncontrollable rate that possesses the ability to infiltrate and destroy normal tissues. It frequently spreads to normal tissues throughout the body, a condition known as metastasis, which is a significant concern. It is the second leading cause of mortality globally and treatment therapy can assist in improving survival rates. Exosomes are the extracellular vesicles secreted by several cells that act as messengers between cells. When enginee ...[more]

PMID: 35551002

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Project description:Exosomes, nanosized membrane vesicles secreted by cardiac progenitor cells (Exo-CPC), inhibit cardiomyocyte apoptosis under stress conditions, promote angiogenesis in vitro, and prevent the early decline in cardiac function after myocardial infarction in vivo in preclinical rat models. The recognition of exosome-mediated effects has moved attempts at developing cell-free approaches for cardiac repair. Such approaches offer major advantages including the fact that exosomes can be stored as ready-to-use agents and delivered to patients with acute coronary syndromes. The aim of the present work was the development of a good manufacturing practice (GMP)-grade method for the large-scale preparation of Exo-CPC as a medicinal product, for a future clinical translation. A GMP-compliant manufacturing method was set up, based on large-scale cell culture in xeno-free conditions, collection of up to 8 l of exosome-containing conditioned medium and isolation of Exo-CPC through tangential flow filtration. Quality control tests were developed and carried out to evaluate safety, identity, and potency of both cardiac progenitor cells (CPC) as cell source and Exo-CPC as final product (GMP-Exo-CPC). CPC, cultured in xeno-free conditions, showed a lower doubling-time than observed in research-grade condition, while producing exosomes with similar features. Cells showed the typical phenotype of mesenchymal progenitor cells (CD73/CD90/CD105 positive, CD14/CD20/CD34/CD45/HLA-DR negative), and expressed mesodermal (TBX5/TBX18) and cardiac-specific (GATA4/MESP1) transcription factors. Purified GMP-Exo-CPC showed the typical nanoparticle tracking analysis profile and expressed main exosome markers (CD9/CD63/CD81/TSG101). The GMP manufacturing method guaranteed high exosome yield (>1013 particles) and consistent removal (≥97%) of contaminating proteins. The resulting GMP-Exo-CPC were tested for safety, purity, identity, and potency in vitro, showing functional anti-apoptotic and pro-angiogenic activity. The therapeutic efficacy was validated in vivo in rats, where GMP-Exo-CPC ameliorated heart function after myocardial infarction. Our standardized production method and testing strategy for large-scale manufacturing of GMP-Exo-CPC open new perspectives for reliable human therapeutic applications for acute myocardial infarction syndrome and can be easily applied to other cell sources for different therapeutic areas.

Dataset Information

Exosomes: Insights and therapeutic applications in cancer.

Publications

Exosomes: Insights and therapeutic applications in cancer.

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