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Journal ArticleDOI

Exosomes for drug delivery - a novel application for the mesenchymal stem cell.

TL;DR: This work proposes human mesenchymal stem cells as the ideal cell source of exosomes for drug delivery, enabling infinite and reproducible exosome production from a single cell clone.
About: This article is published in Biotechnology Advances.The article was published on 2013-09-01. It has received 418 citations till now. The article focuses on the topics: Microvesicles & Homing (hematopoietic).
Citations
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Journal ArticleDOI
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

Journal ArticleDOI
15 Jul 2019-Cells
TL;DR: The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used.
Abstract: The use of extracellular vesicles, specifically exosomes, as carriers of biomarkers in extracellular spaces has been well demonstrated Despite their promising potential, the use of exosomes in the clinical setting is restricted due to the lack of standardization in exosome isolation and analysis methods The purpose of this review is to not only introduce the different types of extracellular vesicles but also to summarize their differences and similarities, and discuss different methods of exosome isolation and analysis currently used A thorough understanding of the isolation and analysis methods currently being used could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality

1,366 citations


Cites background from "Exosomes for drug delivery - a nove..."

  • ...Further, exosomes have a long circulating half-life, are well tolerated by the human body, and capable of not only penetrating cellular membranes but also potentially targeting specific cell types, which makes them an even better candidate for such immunological applications [78]....

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  • ...While methods are still being developed for introduction of RNA and protein to exosomes, and to target these exosomes to a specific region of the body, the ability to load both protein and genetic material into exosomes is yet another advantage making exosomes an attractive drug delivery system [78]....

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Journal ArticleDOI
TL;DR: ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD and has a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders.

1,197 citations


Cites background from "Exosomes for drug delivery - a nove..."

  • ...Moreover, exosomes were harnessed for systemic delivery of exogenous siRNA across the biological barriers [20, 33, 37-39]....

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  • ...In this respect, several reports indicated that exosomes may have an immune privileged status that can efficiently decrease drug clearance [20-22]....

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  • ...Therefore, several investigations suggested harnessing this natural mechanism of protein and genetic material transfer for the delivery of different therapeutics [20, 33-39, 74]....

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Journal ArticleDOI
TL;DR: The origin and structure of exosomes as well as their biological functions are outlined and specific applications of exOSomes as drug delivery systems in pharmaceutical drug development are focused on.

891 citations


Cites background from "Exosomes for drug delivery - a nove..."

  • ...In general, the formation of exosomes consists of three different stages: (1) the formation of endocytic vesicles from plasma membrane, (2) the inward budding of the endosomal vesicle membrane resulting in MVBs that consist of intraluminal vesicles (ILVs), and (3) the fusion of these MVBs with the plasma membrane, which releases the vesicular contents, known as exosomes(7) (Fig....

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Journal ArticleDOI
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

References
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Journal ArticleDOI
02 Apr 1999-Science
TL;DR: Adult stem cells isolated from marrow aspirates of volunteer donors could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages.
Abstract: Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

20,479 citations

Journal ArticleDOI
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


"Exosomes for drug delivery - a nove..." refers background in this paper

  • ...Intercellular transfer of mRNAs by exosomes that resulted in the translation of the transferred mRNA in the recipient cells has also been reported (Valadi et al., 2007)....

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Journal ArticleDOI
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


"Exosomes for drug delivery - a nove..." refers background in this paper

  • ...They have many positive attributes that are pivotal in their function as drug delivery vehicles (reviewed (Torchilin, 2005))....

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  • ...Despite significant advances in the design and efficacy of synthetic liposomes as drug delivery vehicles (Torchilin, 2005), the ideal liposome vehicle that could evade host immune system, be internalized specifically by the target cells, have sufficiently long circulating half-life, minimal…...

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Journal ArticleDOI
15 Feb 2005-Blood
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


"Exosomes for drug delivery - a nove..." refers background in this paper

  • ...…et al., 2002; Le Blanc et al., 2003; Potian et al., 2003; Tse et al., 2003), induce an antiinflammatory tolerant phenotype in dendritic cells (DCs), naive and effector T cells and natural killer (NK) cells (Aggarwal and Pittenger, 2005) and inhibit B cell proliferation (Corcione et al., 2006)....

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Journal ArticleDOI
TL;DR: Tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test by incorporating an mRNA for a reporter protein into them, and it is demonstrated that messages delivered by microvesicle are translated by recipient cells.
Abstract: Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.

4,118 citations