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Nature Nanotechnology Jul 2021Extracellular-vesicle-based cell-to-cell communication is conserved across all kingdoms of life. There is compelling evidence that extracellular vesicles are involved in... (Review)
Review
Extracellular-vesicle-based cell-to-cell communication is conserved across all kingdoms of life. There is compelling evidence that extracellular vesicles are involved in major (patho)physiological processes, including cellular homoeostasis, infection propagation, cancer development and cardiovascular diseases. Various studies suggest that extracellular vesicles have several advantages over conventional synthetic carriers, opening new frontiers for modern drug delivery. Despite extensive research, clinical translation of extracellular-vesicle-based therapies remains challenging. Here, we discuss the uniqueness of extracellular vesicles along with critical design and development steps required to utilize their full potential as drug carriers, including loading methods, in-depth characterization and large-scale manufacturing. We compare the prospects of extracellular vesicles with those of the well established liposomes and provide guidelines to direct the process of developing vesicle-based drug delivery systems.
Topics: Drug Delivery Systems; Extracellular Vesicles; Humans
PubMed: 34211166
DOI: 10.1038/s41565-021-00931-2 -
Advanced Materials (Deerfield Beach,... Jun 2023Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and... (Review)
Review
Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and surface signaling. EVs are secreted by almost all living cells, including plant cells. Plant-derived vesicle-like nanoparticles (PDVLNs) is a generic term referring to vesicle-like nanostructure particles isolated from plants. Their low immunogenicity and wide availability make PDVLNs safer and more economical to be developed as therapeutic agents and drug carriers. Accumulating evidence indicates the key roles of PDVLNs in regulating interkingdom crosstalk between humans and plants. PDVLNs are capable of entering the human-body systemand delivering effector molecules to cells that modulate cell-signaling pathways. PDVLNs released by or obtained from plants thus have great influenceon human health and diseases. In this review, the biogenesis, detailed preparation methods, various physical and biochemical characteristics, biosafety, and preservation of PDVLNs are introduced, along with how these characteristics pertain to their biosafety and preservability. The potential applications of PDVLNs on different plant and mammalian diseases and PDVLN research standardization are then systematically discussed.
Topics: Animals; Humans; Extracellular Vesicles; Plants; Drug Carriers; Cell Communication; Nanoparticles; Mammals
PubMed: 36592157
DOI: 10.1002/adma.202207826 -
Cell Apr 2024In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional...
In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional needs in subcellular compartments but with unknown mechanisms. Such short-distance vesicle transport does not involve molecular motors. Here, we demonstrate, using synaptic vesicle (SV) transport as a paradigm, that phase separation of synaptic proteins with vesicles can facilitate regulated, directional vesicle transport between different presynaptic bouton sub-compartments. Specifically, a large coiled-coil scaffold protein Piccolo, in response to Ca and via its C2A domain-mediated Ca sensing, can extract SVs from the synapsin-clustered reserve pool condensate and deposit the extracted SVs onto the surface of the active zone protein condensate. We further show that the Trk-fused gene, TFG, also participates in COPII vesicle trafficking from ER to the ER-Golgi intermediate compartment via phase separation. Thus, phase separation may play a general role in short-distance, directional vesicle transport in cells.
Topics: Animals; Synaptic Vesicles; COP-Coated Vesicles; Endoplasmic Reticulum; Calcium; Golgi Apparatus; Rats; Biological Transport; Presynaptic Terminals; Synapsins; Biomolecular Condensates; Cytoskeletal Proteins; Phase Separation
PubMed: 38552623
DOI: 10.1016/j.cell.2024.03.003 -
Nature Reviews. Molecular Cell Biology Oct 2020The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment... (Review)
Review
The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications.
Topics: Animals; Biological Transport; Cell Communication; Extracellular Vesicles; Humans; Mammals; RNA
PubMed: 32457507
DOI: 10.1038/s41580-020-0251-y -
Cell Stem Cell Oct 2021During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human...
During embryogenesis, optic vesicles develop from the diencephalon via a multistep process of organogenesis. Using induced pluripotent stem cell (iPSC)-derived human brain organoids, we attempted to simplify the complexities and demonstrate formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day 30, brain organoids attempt to assemble optic vesicles, which develop progressively as visible structures within 60 days. These optic vesicle-containing brain organoids (OVB-organoids) constitute a developing optic vesicle's cellular components, including primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. OVB-organoids also display synapsin-1, CTIP-positive myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photosensitive activity of OVB-organoids, and light sensitivities could be reset after transient photobleaching. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow interorgan interaction studies within a single organoid.
Topics: Cell Differentiation; Embryonic Development; Humans; Induced Pluripotent Stem Cells; Organogenesis; Organoids; Prosencephalon
PubMed: 34407456
DOI: 10.1016/j.stem.2021.07.010 -
Cell Calcium Jun 2023Regulated exocytosis, a universal process of eukaryotic cells, involves the merging between the vesicle membrane and the plasma membrane, plays a key role in...
Regulated exocytosis, a universal process of eukaryotic cells, involves the merging between the vesicle membrane and the plasma membrane, plays a key role in cell-to-cell communication, particularly in the release of hormones and neurotransmitters. There are a number of barriers a vesicle needs to pass to discharge vesicle content to the extracellular space. At the pre-fusion site vesicles need to be transported to the sites on the plasma membrane where the merger may begin. Classically cytoskeleton was considered an important barrier for vesicle translocation and was thought to be disintegrated to allow vesicle access to the plasma membrane [1]. However, it was considered later that cytoskeletal elements may also play a role at the post-fusion stage, promoting the vesicle merger with the plasma membrane and fusion pore expansion [4,22,23]. In this Special Issue of Cell Calcium entitled "Regulated Exocytosis", the authors address outstanding issues related to vesicle chemical messenger release by regulated exocytosis, including that related to the question whether vesicle content discharge is complete or only partial upon the merging of the vesicle membrane with the plasma membrane triggered by Ca. Among processes that limit vesicle discharge at the post-fusion stage is the accumulation of cholesterol in some vesicles [19], a process that has recently been associated with cell aging [20].
Topics: Membrane Fusion; Secretory Vesicles; Cell Membrane; Hormones; Exocytosis
PubMed: 37099857
DOI: 10.1016/j.ceca.2023.102737 -
Nano Letters Jan 2024Extracellular vesicles and lipoproteins are lipid-based biological nanoparticles that play important roles in (patho)physiology. Recent evidence suggests that... (Review)
Review
Extracellular vesicles and lipoproteins are lipid-based biological nanoparticles that play important roles in (patho)physiology. Recent evidence suggests that extracellular vesicles and lipoproteins can interact to form functional complexes. Such complexes have been observed in biofluids from healthy human donors and in various disease models such as breast cancer and hepatitis C infection. Lipoprotein components can also form part of the biomolecular corona that surrounds extracellular vesicles and contributes to biological identity. Potential mechanisms and the functional relevance of extracellular vesicle-lipoprotein complexes remain poorly understood. This Review addresses the current knowledge of the extracellular vesicle-lipoprotein interface while drawing on pre-existing knowledge of liposome interactions with biological nanoparticles. There is an urgent need for further research on the lipoprotein-extracellular vesicle interface, which could return important mechanistic, therapeutic, and diagnostic findings.
Topics: Humans; Lipoproteins; Extracellular Vesicles
PubMed: 38122812
DOI: 10.1021/acs.nanolett.3c03579 -
Current Opinion in Structural Biology Aug 2022Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components... (Review)
Review
Clathrin-mediated endocytosis enables selective uptake of molecules into cells in response to changing cellular needs. It occurs through assembly of coat components around the plasma membrane that determine vesicle contents and facilitate membrane bending to form a clathrin-coated transport vesicle. In this review we discuss recent cryo-electron microscopy structures that have captured a series of events in the life cycle of a clathrin-coated vesicle. Both single particle analysis and tomography approaches have revealed details of the clathrin lattice structure itself, how AP2 may interface with clathrin within a coated vesicle and the importance of PIP2 binding for assembly of the yeast adaptors Sla2 and Ent1 on the membrane. Within cells, cryo-electron tomography of clathrin in flat lattices and high-speed AFM studies provided new insights into how clathrin morphology can adapt during CCV formation. Thus, key mechanical processes driving clathrin-mediated endocytosis have been captured through multiple techniques working in partnership.
Topics: Cell Membrane; Clathrin; Clathrin-Coated Vesicles; Coated Vesicles; Cryoelectron Microscopy; Endocytosis; Saccharomyces cerevisiae
PubMed: 35872561
DOI: 10.1016/j.sbi.2022.102427 -
Journal of Dental Research Dec 2022Hard tissues, including the bones and teeth, are a fundamental part of the body, and their formation and homeostasis are critically regulated by matrix vesicle-mediated... (Review)
Review
Hard tissues, including the bones and teeth, are a fundamental part of the body, and their formation and homeostasis are critically regulated by matrix vesicle-mediated mineralization. Matrix vesicles have been studied for 50 y since they were first observed using electron microscopy. However, research progress has been hampered by various technical barriers. Recently, there have been great advancements in our understanding of the intracellular biosynthesis of matrix vesicles. Mitochondria and lysosomes are now considered key players in matrix vesicle formation. The involvement of mitophagy, mitochondrial-derived vesicles, and mitochondria-lysosome interaction have been suggested as potential detailed mechanisms of the intracellular pathway of matrix vesicles. Their main secretion pathway may be exocytosis, in addition to the traditionally understood mechanism of budding from the outer plasma membrane. This basic knowledge of matrix vesicles should be strengthened by novel nano-level microscopic technologies, together with basic cell biologies, such as autophagy and interorganelle interactions. In the field of tissue regeneration, extracellular vesicles such as exosomes are gaining interest as promising tools in cell-free bone and periodontal regenerative therapy. Matrix vesicles, which are recognized as a special type of extracellular vesicles, could be another potential alternative. In this review, we outline the recent significant progress in the process of matrix vesicle-mediated mineralization and the potential clinical applications of matrix vesicles for tissue regeneration.
Topics: Calcification, Physiologic; Bone and Bones; Extracellular Vesicles; Exosomes; Autophagy; Extracellular Matrix
PubMed: 35722955
DOI: 10.1177/00220345221103145 -
Nature Reviews. Materials Jun 2023The extracellular matrix in microenvironments harbors a variety of signals to control cellular functions and the materiality of tissues. Most efforts to synthetically...
The extracellular matrix in microenvironments harbors a variety of signals to control cellular functions and the materiality of tissues. Most efforts to synthetically reconstitute the matrix by biomaterial design have focused on decoupling cell-secreted and polymer-based cues. Cells package molecules into nanoscale lipid membrane-bound extracellular vesicles and secrete them. Thus, extracellular vesicles inherently interact with the meshwork of the extracellular matrix. In this Review, we discuss various aspects of extracellular vesicle-matrix interactions. Cells receive feedback from the extracellular matrix and leverage intracellular processes to control the biogenesis of extracellular vesicles. Once secreted, various biomolecular and biophysical factors determine whether extracellular vesicles are locally incorporated into the matrix or transported out of the matrix to be taken up by other cells or deposited into tissues at a distal location. These insights can be utilized to develop engineered biomaterials where EV release and retention can be precisely controlled in host tissue to elicit various biological and therapeutic outcomes.
PubMed: 38463907
DOI: 10.1038/s41578-023-00551-3