The Biology and Therapeutic Applications of Red Blood Cell Extracellular Vesicles

This chapter focuses on the biology of red blood cell extracellular vesicles (RBCEVs) in normal and diseased conditions, and the potential application of RBCEVs in treatment. Extracellular vesicles (EVs) refer to membranous vesicles secreted by cells into the extracellular environment. EV biology belongs to a rapidly developing field in biomedical sciences. EVs represent a natural mode of cell-to-cell communication, which makes them suitable for delivery of therapeutic agents, such as nucleic acids and proteins, in the body. In particular, RBCEVs feature a wide range of benefits in drug delivery as compared to extracellular vesicles derived from other cell types. In comparison to other delivery systems currently available, RBCEVs are nontoxic, low immunogenic, conveniently obtainable, and easy to use and store. Therefore, RBCEVs boast promising and exceptional advantages in overcoming various limitations of conventional therapeutics

MicroRNA-29 specifies age-related differences in the CD8+ T cell immune response

MicroRNAs (miRNAs) have emerged as critical regulators of cell fate in the CD8+ T cell response to infection. Although there are several examples of miRNAs acting on effector CD8+ T cells after infection, it is unclear whether differential expression of one or more miRNAs in the naive state is consequential in altering their long-term trajectory. To answer this question, we examine the role of miR-29 in neonatal and adult CD8+ T cells, which express different amounts of miR-29 only prior to infection and adopt profoundly different fates after immune challenge. We find that manipulation of miR-29 expression in the naive state is sufficient for age-adjusting the phenotype and function of CD8+ T cells, including their regulatory landscapes and long-term differentiation trajectories after infection. Thus, miR-29 acts as a developmental switch by controlling the balance between a rapid effector response in neonates and the generation of long-lived memory in adults

Small but mighty: microRNAs as novel signalling molecules in cancer: DOI: 10.14800/rd.627

microRNAs (miRNAs) are short, noncoding RNAs that silence target messenger RNAs by blocking translation or promoting transcript degradation. While the roles of miRNAs within cells have been extensively characterized, emerging evidence suggests that miRNAs are also transported between cells, providing a novel form of intercellular communication. Circulating miRNAs have been identified, packaged in extracellular vesicles or associated with high-density lipoproteins and Argonaute proteins. Specific extracellular miRNAs have been associated with human cancers. They not only serve as measurable disease biomarkers, but recent findings suggest secreted miRNAs may also mediate crosstalk between cancer cells and other cell types, including those that comprise the prometastatic tumor niche. Previous studies, reviewed here, demonstrate that miRNAs released by cancer cells can be internalized by nearby or distant cells, to modify gene expression and alter the tumor microenvironment. As critical drivers of both oncogenesis and metastasis, miRNAs may be attractive therapeutic targets in a wide range of cancers

Extracellular vesicles and lipoproteins – Smart messengers of blood cells in the circulation

Abstract Blood cell‐derived extracellular vesicles (BCEVs) and lipoproteins are the major circulating nanoparticles in blood that play an important role in intercellular communication. They have attracted significant interest for clinical applications, given their endogenous characteristics which make them stable, biocompatible, well tolerated, and capable of permeating biological barriers efficiently. In this review, we describe the basic characteristics of BCEVs and lipoproteins and summarize their implications in both physiological and pathological processes. We also outline well accepted workflows for the isolation and characterization of these circulating nanoparticles. Importantly, we highlight the latest progress and challenges associated with the use of circulating nanoparticles as diagnostic biomarkers and therapeutic interventions in multiple diseases. We spotlight novel engineering approaches and designs to facilitate the development of these nanoparticles by enhancing their stability, targeting capability, and delivery efficiency. Therefore, the present work provides a comprehensive overview of composition, biogenesis, functions, and clinical translation of circulating nanoparticles from the bench to the bedside