Unlocking the potential of EXOs in regenerative medicine: A comprehensive review

Extracellular vesicles (EVs), particularly exosomes (EXOs), are essential in cellular communication and play significant roles in various physiological and pathological processes. Ranging in size from 30 to 150 nm, EXOs are lipid vesicles derived from the endosomal system and characterized by their distinctive cup-shaped morphology. These vesicles are produced by hematopoietic and non-hematopoietic cells and are found in all body fluids, including blood plasma, cerebrospinal fluid, urine, saliva, and breast milk. EXOs are equipped to transfer a myriad of bioactive materials-proteins, lipids, nucleic acids, and microRNAs-to recipient cells locally and distantly, potentially altering cellular function and influencing the microenvironment. Given their significant roles, this review comprehensively examines the various aspects of EXOs, from their biogenesis and preparation to their isolation and detailed characterization. We discuss the necessity of understanding these fundamental aspects to harness EXOs' potential in clinical applications, particularly in regenerative medicine. The review highlights the latest advances in using EXOs as carriers for therapeutic molecules, ranging from small molecules and genes to large therapeutic proteins and nanoparticles, emphasizing their application in drug delivery for cancer treatment and immunotherapy. Moreover, the paper delves into the promising applications of EXOs in tissue repair and regeneration, detailing specific cases in skin, bone, cartilage, heart, lung, and neurological diseases, among others. Each section explores not only the therapeutic potential but also the underlying mechanisms by which EXOs facilitate these regenerative processes. By discussing the clinical applications and inherent challenges of utilizing EXOs, this review underscores the critical need for continued research to fully exploit EXOs' therapeutic capabilities, offering insights into their future implications in medicine.