Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery☆
TL;DR: Of the cell types known to produce exosomes, the readily available proliferative, immunosuppressive and clinically tested human mesenchymal stem cell (MSC) is the most prolific producer.
About: This article is published in Advanced Drug Delivery Reviews.The article was published on 2013-03-01. It has received 620 citations till now.
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TL;DR: The intrinsic properties of exosomes in regulating complex intracellular pathways has advanced their potential utility in the therapeutic control of many diseases, including neurodegenerative conditions and cancer.
Abstract: The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
3,715 citations
TL;DR: Recent progress in understanding extracellular vesicle biology and the role of extrace cellular vesicles in disease is reviewed, emerging therapeutic opportunities are discussed and the associated challenges are considered.
Abstract: Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.
2,507 citations
TL;DR: This article aims to present a comprehensive and critical overview of emerging analytical technologies for EV detection and their clinical applications.
Abstract: Extracellular vesicles (EVs) are diverse, nanoscale membrane vesicles actively released by cells Similar-sized vesicles can be further classified (eg, exosomes, microvesicles) based on their biogenesis, size, and biophysical properties Although initially thought to be cellular debris, and thus under-appreciated, EVs are now increasingly recognized as important vehicles of intercellular communication and circulating biomarkers for disease diagnoses and prognosis Despite their clinical potential, the lack of sensitive preparatory and analytical technologies for EVs poses a barrier to clinical translation New analytical platforms including molecular ones are thus actively being developed to address these challenges Recent advances in the field are expected to have far-reaching impact in both basic and translational studies This article aims to present a comprehensive and critical overview of emerging analytical technologies for EV detection and their clinical applications
902 citations
TL;DR: Current knowledge related to the potential use of MSC-derived EVs in various diseases is reviewed and the promising future for EVs as an alternative, cell-free therapy is discussed.
783 citations
TL;DR: The current understanding of physiological and pathophysiological roles of exosomes, their potential applications as diagnostic markers, and current efforts to develop improved exosome‐based drug delivery systems are reviewed.
690 citations
Cites background from "Mesenchymal stem cell: An efficient..."
...cytoprotective activities of their parent cells (Baglio et al., 2012; Yeo et al., 2013)....
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...…response Recruiting Cancer Europe Blood NCT02439008 Evaluation of MicroRNA expression in blood and cytology for detecting Barrett's esophagus and associated neoplasia Recruiting Cancer USA Bile NCT02464930 cytoprotective activities of their parent cells (Baglio et al., 2012; Yeo et al., 2013)....
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References
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TL;DR: The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC, believing this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.
14,724 citations
"Mesenchymal stem cell: An efficient..." refers methods in this paper
...The International Society for Cellular Therapy position statement, Cytotherapy 8 (2006) 315–317....
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...According to the minimal defining criteria by International Society for Cellular Therapy [40], MSCs must be plastic-adherent when maintained in standard culture conditions; they must express CD105, CD73 and CD90 and not express CD45, CD34, CD14 or CD11b, CD79α or CD19 and HLA-DR surface molecules....
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TL;DR: It is shown that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location, and it is proposed that this RNA is called “exosomal shuttle RNA” (esRNA).
Abstract: Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).
10,484 citations
"Mesenchymal stem cell: An efficient..." refers background in this paper
...Exosomes have also been shown tomediate intercellular transfer of mRNAs and miRNAs that resulted in the translation of the transferred mRNA in the recipient cells [47]....
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TL;DR: For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.
Abstract: Liposomes — microscopic phospholipid bubbles with a bilayered membrane structure — have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs — from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.
4,572 citations
"Mesenchymal stem cell: An efficient..." refers background in this paper
...Liposomes havemany positive attributes that are pivotal in their function as drug delivery vehicles (reviewed in [14])....
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TL;DR: The physical properties that define exosomes as a specific population of secreted vesicles are described, their biological effects, particularly on the immune system, are summarized, and the potential roles that secretedvesicles could have as intercellular messengers are discussed.
Abstract: Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture. Interest in exosomes has intensified after their recent description in antigen-presenting cells and the observation that they can stimulate immune responses in vivo. In the past few years, several groups have reported the secretion of exosomes by various cell types, and have discussed their potential biological functions. Here, we describe the physical properties that define exosomes as a specific population of secreted vesicles, we summarize their biological effects, particularly on the immune system, and we discuss the potential roles that secreted vesicles could have as intercellular messengers.
4,380 citations
TL;DR: Insight is offered into the interactions between allogeneic MSCs and immune cells and mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.
4,264 citations
"Mesenchymal stem cell: An efficient..." refers background in this paper
...MSCs inhibit proliferation of mitogen-activated T cells [110–114], induce an anti-inflammatory tolerant phenotype in dendritic cells (DCs), naive and effector T cells and natural killer (NK) cells [115] and in-...
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