Concise Review: MSC-Derived Exosomes for Cell-Free Therapy

Stem Cells, Год журнала: 2017, Номер 35(4), С. 851 - 858

Опубликована: Март 10, 2017

Abstract Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion vitro there natural desire test many diverse indications. This exemplified by the rapidly expanding literature base that includes vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes microvesicles (MV), being examined for their role MSC-based therapy. These involved cell-to-cell communication, signaling, altering or tissue metabolism at short long distances body. The MVs can influence responses injury, infection, disease. have content cytokines growth factors, signaling lipids, mRNAs, regulatory miRNAs. To extent MSC be used cell-free regenerative medicine, much will depend on quality, reproducibility, potency of production, same manner these parameters dictate development cell-based therapies. However, exosome's contents not static, but rather product origin, its activities immediate intercellular neighbors MSCs. As such, exosome produced appears altered when cultured with tumor cells microenvironment. Therefore, careful attention detail producing may provide new therapeutic paradigm therapies decreased risk.

Язык: Английский

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Extracellular vesicles in cancer — implications for future improvements in cancer care

Nature Reviews Clinical Oncology, Год журнала: 2018, Номер 15(10), С. 617 - 638

Опубликована: Май 23, 2018

Язык: Английский

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Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory

Cell, Год журнала: 2019, Номер 177(2), С. 414 - 427.e13

Опубликована: Апрель 1, 2019

PD-L1 on the surface of tumor cells binds its receptor PD-1 effector T cells, thereby suppressing their activity. Antibody blockade can activate an anti-tumor immune response leading to durable remissions in a subset cancer patients. Here, we describe alternative mechanism activity involving secretion tumor-derived exosomes. Removal exosomal inhibits growth, even models resistant anti-PD-L1 antibodies. Exosomal from suppresses cell activation draining lymph node. Systemically introduced rescues growth tumors unable secrete own. Exposure PD-L1-deficient wild-type injected at distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with suppress growth. Together, these findings show that represents unexplored therapeutic target, which could overcome resistance current antibody approaches.

Язык: Английский

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Isolation of Extracellular Vesicles: General Methodologies and Latest Trends

BioMed Research International, Год журнала: 2018, Номер 2018, С. 1 - 27

Опубликована: Янв. 1, 2018

Background . Extracellular vesicles (EVs) play an essential role in the communication between cells and transport of diagnostically significant molecules. A wide diversity approaches utilizing different biochemical properties EVs a lack accepted protocols make data interpretation very challenging. Scope Review This review consolidates on classical state-of-the-art methods for isolation EVs, including exosomes, highlighting advantages disadvantages each method. Various characteristics individual methods, efficiency, EV yield, isolated labor consumption are compared. Major Conclusions mixed population is obtained most studies all used methods. The analyzed sample should be taken into account when planning experiment aimed at studying using these vesicles. problem adequate still remains; it might not possible to develop universal method but available can towards solving particular types problems. General Significance With use diagnosis therapy various diseases evaluation existing one key problems modern biology medicine.

Язык: Английский

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Exosomes: Therapy delivery tools and biomarkers of diseases

Pharmacology & Therapeutics, Год журнала: 2017, Номер 174, С. 63 - 78

Опубликована: Фев. 13, 2017

Язык: Английский

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Exosomes: key players in cancer and potential therapeutic strategy

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Авг. 5, 2020

Exosomes are extracellular vesicles secreted by most eukaryotic cells and participate in intercellular communication. The components of exosomes, including proteins, DNA, mRNA, microRNA, long noncoding RNA, circular etc., which play a crucial role regulating tumor growth, metastasis, angiogenesis the process cancer development, can be used as prognostic marker and/or grading basis for patients. Hereby, we mainly summarized followed: exosome contents cancer, focusing on proteins RNA; interaction between exosomes microenvironment; mechanisms that epithelial-mesenchymal transition, invasion migration affected exosomes; suppression strategies based exosomes. Finally, application potential clinical diagnosis therapy is prospected, providing theoretical supports using to serve precise treatment clinic.

Язык: Английский

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Methodological Guidelines to Study Extracellular Vesicles

Circulation Research, Год журнала: 2017, Номер 120(10), С. 1632 - 1648

Опубликована: Май 11, 2017

Owing to the relationship between extracellular vesicles (EVs) and physiological pathological conditions, interest in EVs is exponentially growing. hold high hopes for novel diagnostic translational discoveries. This review provides an expert-based update of recent advances methods study summarizes currently accepted considerations recommendations from sample collection isolation, detection, characterization EVs. Common misconceptions methodological pitfalls are highlighted. Although found all body fluids, this review, we will focus on human blood, not only our most complex but also interesting fluid cardiovascular research.

Язык: Английский

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Application of exosomes as liquid biopsy in clinical diagnosis

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Авг. 3, 2020

Liquid biopsy refers to the sampling and molecular analysis of biofluids circulating tumor cells, extracellular vesicles, nucleic acids, so forth. Exosomes are small vesicles with sizes between 30-150 nm. They secreted by multivesicular bodies through exocytosis in live cells can participate intercellular communication due their contents, including proteins, lipids. Herein, we investigate publication frequencies on exosomes over past 10 years, review recent clinical studies liquid fields oncology, pregnancy disorders, cardiovascular diseases, organ transplantation. We also describe advantages as an effective tool progression exosome extraction methods. Finally, depict commercial development research discuss future role biopsy.

Язык: Английский

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Efficient RNA drug delivery using red blood cell extracellular vesicles

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Июнь 11, 2018

Most of the current methods for programmable RNA drug therapies are unsuitable clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode intercellular communication. However, cellular sources EV production limited in availability safety terms horizontal gene transfer. One potentially ideal source be human red blood cells (RBCs). Group O-RBCs can used as universal donors large-scale since readily available banks devoid DNA. Here, we describe validate new strategy generate amounts RBC-derived EVs delivery drugs, including antisense oligonucleotides, Cas9 mRNA, guide RNAs. with RBCEVs shows highly robust microRNA inhibition CRISPR-Cas9 genome editing both xenograft mouse models, no observable

Язык: Английский

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Extracellular vesicles: masters of intercellular communication and potential clinical interventions

Journal of Clinical Investigation, Год журнала: 2016, Номер 126(4), С. 1139 - 1143

Опубликована: Март 31, 2016

Intercellular signaling via extracellular vesicles (EVs) is an underappreciated modality of cell-cell crosstalk that enables cells to convey packages complex instructions specific recipient cells. EVs transmit these through their cargoes multiple proteins, nucleic acids, and specialized lipids, which are derived from origin allow for combinatorial effects upon This Review series brings together the recent progress in our understanding EV physiological pathophysiological conditions, highlighting how certain EVs, particularly exosomes, can promote or regulate infections, host immune responses, development, various diseases - notably cancer. Given diverse nature abilities profoundly modulate cells, this puts particular emphasis on clinical applications as therapeutics diagnostic biomarkers.

Язык: Английский

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