Unleashing the therapeutic potential of apoptotic bodies

Abstract

Extracellular vesicles (EVs), membrane-bound vesicles that are naturally released by cells, have emerged as new therapeutic opportunities. EVs, particularly exosomes and microvesicles, can transfer effector molecules and elicit potent responses in recipient cells, making them attractive therapeutic targets and drug delivery platforms. Furthermore, containing predictive biomarkers and often being dysregulated in various disease settings, these EVs are being exploited for diagnostic purposes. In contrast, the therapeutic application of apoptotic bodies (ApoBDs), a distinct type of EVs released by cells undergoing a form of programmed cell death called apoptosis, has been largely unexplored. Recent studies have shed light on ApoBD biogenesis and functions, promisingly implicating their therapeutic potential. In this review, we discuss many strategies to develop ApoBD-based therapies as well as highlight their advantages and challenges, thereby positioning ApoBD for potential EV-based therapy.

Mesenchymal stromal cell apoptosis is required for their therapeutic function

“…extracellular vesicles) offer an attractive cell-free therapeutic alternative, they may not be a direct measure of potency when viable MSCs are infused as a cellular product. On the other hand, apoptotic MSC-derived extracellular vesicles have recently been shown to demonstrate therapeutic potential 47 , 69 – 71 . Our data provide further understanding of the mechanisms of MSC therapy and reveal opportunities for novel therapeutic interventions.…”

Pannexin‐1 channel regulates nuclear content packaging into apoptotic bodies and their size

“…In these particular settings, by pharmacologically targeting PANX1 using inhibitors such as trovafloxacin during the production of these tumor nuclear antigens encapsulated ApoBDs, the quantity (through enhancing ApoBD production) and quality (through elevated nuclear antigen sorting) may be improved. Using similar approach, as ApoBDs hold potential as a drug delivery system [3], therapeutic nuclear proteins, such as nuclear resident transcription factors [42], could be efficiently loaded onto ApoBDs by engineering them into host cells followed by apoptosis induction and PANX1 inhibitor treatments.…”

“…Apoptosis (a form of programmed cell death) occurs as a vital part of homeostasis and physiopathology such as chronic inflammation and infection [1,2]. Cells undergoing apoptosis often release apoptotic bodies (ApoBDs), a distinct type of membrane-bound extracellular vesicles (EVs) generally considered as 1-5 μm in size, to communicate Abbreviations: ApoBDs, apoptotic bodies; EV, extracellular vesicle; GO, gene ontology; HMGA1, high mobility group protein A1; NUP50, 50 kD nucleoporin; PANX1, pannexin 1; THYN1, thymocyte nuclear protein 1 with other cells to regulate cell clearance, tissue repair and/or immune response [3]. In contrast to previously thought, ApoBD formation is a highly co-ordinated process known as apoptotic cell disassembly consisting of three morphological steps: (i) membrane blebbing, (ii) thin membrane protrusions (e.g., apoptopodia), and (iii) fragmentation to form discrete ApoBDs.…”

“…Despite current modest knowledge of ApoBD functions, it is becoming clear that ApoBDs also possess a few similar therapeutically exploitable properties compared to other EV subtypes [3]. Particularly, ApoBDs are readily available and easily purified from bodily fluids [9,10].…”

Microglial Extracellular Vesicles as Vehicles for Neurodegeneration Spreading

“…These blebs then extend radially forming long protrusions with engulfed cellular components. The bleb elongation process is regulated by other caspase-activated proteins, caspase-activated membrane channel pannexin 1 (PANX1) that negatively regulates bleb formation or in some cell types caspase-cleaved membrane receptor plexin B2 (PLXB2) that favors bleb elongation [ 103 , 104 ]. The disassembly of PANX1 promotes the release of apoptotic bodies from the dying cell through the fragmentation of the cellular structure [ 105 ].…”