In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

/pdf/biological-properties-of-extracellular-vesicles-and-their-bef7axtqvb.pdf

Biological properties of extracellular vesicles and their physiological functions

Mesenchymal stem/stromal cells (MSCs) are increasingly used as an intravenously applied cellular therapeutic. They were found to be potent in situations such as tissue repair or severe inflammation. Still, data are lacking with regard to the biodistribution of MSCs, their cellular or molecular target structures, and the mechanisms by which MSCs reach these targets. This review discusses current hypotheses for how MSCs can reach tissue sites. Both preclinical and clinical studies using MSCs applied intravenously or intra-arterially are discussed in the context of our current understanding of how MSCs might work in physiological and pathological situations.

/pdf/biodistribution-migration-and-homing-of-systemically-applied-3rulbige2p.pdf

Biodistribution, migration and homing of systemically applied mesenchymal stem/stromal cells

Mesenchymal stem cells (MSCs) are promising candidates for adult cell therapies in regenerative medicine To fully exert their potential, efficient homing and migration toward lesion sites play an important role Local transplantation deposits MSC in spatial proximity to the lesion, but often requires invasive procedures Systemic administration routes are favored, but require the targeted extravasation of the circulating MSC at the site of injury Transplanted MSC can indeed leave the blood flow and transmigrate through the endothelial barrier, and reach the lesion site However, the underlying processes are not completely dissolved yet Recent in vitro and in vivo research identified some key molecules scattered light on the extravasation mechanism This review provides a detailed overview over the current knowledge of MSC transendothelial migration We use the leukocyte extravasation process as a role model to build a comprehensive concept of MSC egress mechanisms from the blood stream and identified relevant similarities as well as important differences between the extravasation mechanisms Stem Cells 2017;35:1446-1460

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/stem.2614

Concise Review: MSC Adhesion Cascade—Insights into Homing and Transendothelial Migration

Protein sequencing and identification using tandem mass spectrometry. Edited by Michael Kinter, Nicholas E. Sherman, published by Wiley-Interscience Series on Mass Spectrometry, 2000, 301 p.

Click chemistry has great potential for use in binding between nucleic acids, lipids, proteins, and other molecules, and has been used in many research fields because of its beneficial characteristics, including high yield, high specificity, and simplicity. The recent development of copper-free and less cytotoxic click chemistry reactions has allowed for the application of click chemistry to the field of medicine. Moreover, metabolic glycoengineering allows for the direct modification of living cells with substrates for click chemistry either in vitro or in vivo. As such, click chemistry has become a powerful tool for cell transplantation and drug delivery. In this review, we describe some applications of click chemistry for cell engineering in cell transplantation and for drug delivery in the diagnosis and treatment of diseases.

Click Chemistry as a Tool for Cell Engineering and Drug Delivery

Systemic infusion of therapeutic cells would be the most practical and least invasive method of administration in many cellular therapies. One of the main obstacles especially in intravenous delivery of cells is a massive cell retention in the lungs, which impairs homing to the target tissue and may decrease the therapeutic outcome. In this study we showed that an alternative cell detachment of mesenchymal stromal/stem cells (MSCs) with pronase instead of trypsin significantly accelerated the lung clearance of the cells and, importantly, increased their targeting to an area of injury. Cell detachment with pronase transiently altered the MSC surface protein profile without compromising cell viability, multipotent cell characteristics, or immunomodulative and angiogenic potential. The transient modification of the cell surface protein profile was sufficient to produce effective changes in cell rolling behavior in vitro and, importantly, in the in vivo biodistribution of the cells in mouse, rat, and porcine models. In conclusion, pronase detachment could be used as a method to improve the MSC lung clearance and targeting in vivo. This may have a major impact on the bioavailability of MSCs in future therapeutic regimes.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.5966/sctm.2012-0187

Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue

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Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue