Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain
TL;DR: It is demonstrated in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the blood-brain barrier and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain.
About: This article is published in Biomaterials.The article was published on 2017-10-01 and is currently open access. It has received 354 citations till now. The article focuses on the topics: Nanoparticles for drug delivery to the brain & Microvesicles.
Citations
More filters
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
Cites background from "Macrophage exosomes as natural nano..."
...Macrophagederived exosomes show the capacity to effectively negotiate the blood–brain barrier and deliver protein cargo (231), supporting the idea that minimal modification of exosomes is required to reach the brain parenchyma....
[...]
TL;DR: The manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration of PTX-loaded exosomes with incorporated aminoethylanisamide-polyethylene glycol vector moiety to target the sigma receptor, which is overexpressed by lung cancer cells is reported.
405 citations
TL;DR: The current state-of-the-art of using exosomes or exosome-inspired systems for drug delivery is provided and the various approaches investigated and the shortcomings of each approach are reviewed.
Abstract: The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here, we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges which have been identified to date in this field are summarized.
366 citations
Cites background from "Macrophage exosomes as natural nano..."
...Thereby, naïve macrophage-derived exosomes can function as nanocarriers for brain delivery of therapeutic proteins to treat CNS diseases [175]....
[...]
TL;DR: A review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell is provided in this paper.
Abstract: Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.
350 citations
TL;DR: The evidence that exosomes could be used as a neurorestorative therapy after stroke or traumatic brain injury is discussed and how engineering of their microRNA cargo could optimize this approach.
Abstract: Stroke is a leading cause of disability worldwide, and brain injuries devastate patients and their families, but currently no drugs on the market promote neurological recovery. Limited spontaneous recovery of function as a result of brain remodelling after stroke or injury does occur, and cell-based therapies have been used to promote these endogenous processes. Increasing evidence is demonstrating that the positive effects of such cell-based therapy are mediated by exosomes released from the administered cells and that the microRNA cargo in these exosomes is largely responsible for the therapeutic effects. This evidence raises the possibility that isolated exosomes could be used alone as a neurorestorative therapy and that these exosomes could be tailored to maximize clinical benefit. The potential of exosomes as a therapy for brain disorders is therefore being actively investigated. In this Review, we discuss the current knowledge of exosomes and advances in our knowledge of their effects on endogenous neurovascular remodelling events. We also consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy.
298 citations
References
More filters
TL;DR: The origins, challenges and solutions of NIH Image and ImageJ software are discussed, and how their history can serve to advise and inform other software projects.
Abstract: For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
44,587 citations
"Macrophage exosomes as natural nano..." refers methods in this paper
...Mander’s colocalization coefficients were calculated using Image J and JACoP plugin [24, 25]....
[...]
TL;DR: This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosomes preparations.
Abstract: Exosomes are small membrane vesicles found in cell culture supernatants and in different biological fluids. Exosomes form in a particular population of endosomes, called multivesicular bodies (MVBs), by inward budding into the lumen of the compartment. Upon fusion of MVBs with the plasma membrane, these internal vesicles are secreted. Exosomes possess a defined set of membrane and cytosolic proteins. The physiological function of exosomes is still a matter of debate, but increasing results in various experimental systems suggest their involvement in multiple biological processes. Because both cell-culture supernatants and biological fluids contain different types of lipid membranes, it is critical to perform high-quality exosome purification. This unit describes different approaches for exosome purification from various sources, and discusses methods to evaluate the purity and homogeneity of the purified exosome preparations.
4,492 citations
"Macrophage exosomes as natural nano..." refers background or methods in this paper
...Protein composition and exosomal markers were detected by standard sodium d odecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting und er reducing condition [23]....
[...]
...Based on SDS-PAGE, the protein composition of exosomes differed from both the parent Mφs and FBS [23]....
[...]
...The conditioned medium for exosome collection was DMEM plus 1% penicillin-streptomycin and M AN US CR IP T AC CE PT ED 10% FBS pre-centrifuged at 120 kg for 140 min to remove serum exosomes. hCMEC/D3 cells (a kind gift from Dr. Pierre-Olivier Couraud in Cochin I stitute, France) between passage 30 and 35 were used....
[...]
...The cells were grown in DMEM medium plus 10% FBS and 1% penicillin-streptomycin, a d subcultured by scraping....
[...]
...The cells were grown in EBM-2 containing 5% FBS, 1% Penicillin-Streptomycin, 1.4 µM hydrocortisone, 5µg/ml acid ascorbic, 100× diluted chemically defined lipid concentrate, 10 mM HEPES and 1 ng/ml bFGF ....
[...]
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
"Macrophage exosomes as natural nano..." refers background in this paper
...However, exosomes pres ent major histocompatibility complex (MHC) molecules and a co-stimulatory molecule CD86 on the surface, which can potentially boost the immune response, especially with chronic exposure [9, 10]....
[...]
TL;DR: A novel toolbox for subcellular colocalization analysis under ImageJ is created that integrates current global statistic methods and a novel object‐based approach to assess proteins residing on intracellular structures by fluorescence microscopy.
Abstract: Summary It is generally accepted that the functional compartmentalization of eukaryotic cells is reflected by the differential occurrence of proteins in their compartments. The location and physiological function of a protein are closely related; local information of a protein is thus crucial to understanding its role in biological processes. The visualization of proteins residing on intracellular structures by fluorescence microscopy has become a routine approach in cell biology and is increasingly used to assess their colocalization with well-characterized markers. However, imageanalysis methods for colocalization studies are a field of contention and enigma. We have therefore undertaken to review the most currently used colocalization analysis methods, introducing the basic optical concepts important for image acquisition and subsequent analysis. We provide a summary of practical tips for image acquisition and treatment that should precede proper colocalization analysis. Furthermore, we discuss the application and feasibility of colocalization tools for various biological colocalization situations and discuss their respective strengths and weaknesses. We have created a novel toolbox for subcellular colocalization analysis under Image J, named JACoP, that integrates current global statistic methods and a novel object-based approach.
4,195 citations
"Macrophage exosomes as natural nano..." refers methods in this paper
...Mander’s colocalization coefficients were calculated using Image J and JACoP plugin [24, 25]....
[...]
TL;DR: A theoretical model of blood–brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period.
Abstract: A theoretical model of blood-brain exchange is developed and a procedure is derived that can be used for graphing multiple-time tissue uptake data and determining whether a unidirectional transfer process was dominant during part or all of the experimental period. If the graph indicates unidirectionality of uptake, then an influx constant (Ki) can be calculated. The model is general, assumes linear transfer kinetics, and consists of a blood-plasma compartment, a reversible tissue region with an arbitrary number of compartments, and one or more irreversible tissue regions. The solution of the equations for this model shows that a graph of the ratio of the total tissue solute concentration at the times of sampling to the plasma concentration at the respective times (Cp) versus the ratio of the arterial plasma concentration-time integral to Cp should be drawn. If the data are consistent with this model, then this graph will yield a curve that eventually becomes linear, with a slope of Ki and an ordinate intercept less than or equal to the vascular plus steady-state space of the reversible tissue region.
3,526 citations
"Macrophage exosomes as natural nano..." refers methods in this paper
...The Ki (slope) and (yintercept) were calculated from the linear portion f multiple-time regression analysis [27]....
[...]