Apoptotic bodies: bioactive treasure left behind by the dying cells with robust diagnostic and therapeutic application potentials

Abstract

Apoptosis, a form of programmed cell death, is essential for growth and tissue homeostasis. Apoptotic bodies (ApoBDs) are a form of extracellular vesicles (EVs) released by dying cells in the last stage of apoptosis and were previously regarded as debris of dead cells. Recent studies unraveled that ApoBDs are not cell debris but the bioactive treasure left behind by the dying cells with an important role in intercellular communications related to human health and various diseases. Defective clearance of ApoBDs and infected-cells-derived ApoBDs are possible etiology of some diseases. Therefore, it is necessary to explore the function and mechanism of the action of ApoBDs in different physiological and pathological conditions. Recent advances in ApoBDs have elucidated the immunomodulatory, virus removal, vascular protection, tissue regenerative, and disease diagnostic potential of ApoBDs. Moreover, ApoBDs can be used as drug carriers enhancing drug stability, cellular uptake, and targeted therapy efficacy. These reports from the literature indicate that ApoBDs hold promising potential for diagnosis, prognosis, and treatment of various diseases, including cancer, systemic inflammatory diseases, cardiovascular diseases, and tissue regeneration. This review summarizes the recent advances in ApoBDs-related research and discusses the role of ApoBDs in health and diseases as well as the challenges and prospects of ApoBDs-based diagnostic and therapeutic applications. Graphical Abstract

Efferocytosis by macrophages in physiological and pathological conditions: regulatory pathways and molecular mechanisms

“…Another study reported that AC removal by macrophages limited the release of thromboxane-B2 ( 57 ). Gradually, researchers began to regard the apoptotic cargos as “bioactive treasures” released from dying cells, which promoted a pro-resolving macrophage phenotype ( 58 ). Efferocytosis enables anti-inflammatory and homeostatic maintenance.…”

A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment

“…The biogenesis of apoptotic bodies starts with the initiation of cell apoptosis, which requires chromatin condensation, nuclear shattering, and cell shrinking, with the concomitant formation of blebs, which constitute the so-called microtubule spikes, as well as the apoptopodia. At the end of this procedure, the apoptotic vesicles are formed, after the segmentation of the apoptotic bodies [ 21 ].…”

Emerging role of extracellular vesicles in diabetic retinopathy

“…On the other hand, ectosomes are vesicles ranging from 50 nm to 10000 nm that are directly shed from the plasma membrane of both healthy and damaged cells 8 . While apoptotic bodies, one of the most well-studied subtypes of ectosomes, are submicron vesicles only derived from cells undergoing programmed cell death 9 . Recently, membranous vesicles produced by migrating cells at the near ends are identified as a novel subtype of EVs and referred to as “migrasome”, whose roles in cellular communication are under extensive exploration 10 , 11 .…”