Engineered Mesenchymal Stem Cell-Derived Extracellular Vesicles as Antifibrotic Nanotherapeutics for Chronic Kidney Disease.

Chronic kidney disease (CKD) affects more than 850 million people worldwide, and progressive renal fibrosis is the most common cause of irreversible renal loss. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are nanoscale membrane-bound particles carrying bioactive proteins, lipids, and regulatory RNAs across biological barriers. Target cells are EVs that enter via membrane receptors and endocytic/fusion pathways and provide cargo delivery and modulation of downstream signaling. Engineering techniques such as genetic modification of parent cells, chemical surface functionalization, stimuli-responsive materials, and synthetic materials have improved the therapeutic potential of MSC-EVs by improving tissue targeting and antifibrotic activity. This review summarizes MSC-EV colloidal biology, biogenesis, surface properties, cargo composition, and engineered modifications for antifibrotic applications. Mechanisms that inhibit fibrosis, such as suppression of the TGF-β/Smad pathway, reversal of epithelial-mesenchymal transition, and modulation of macrophage behavior at the tissue-vesicle interface, are discussed. Effects of donor cell preconditioning and microenvironmental factors on surface properties and therapeutic potency are discussed. This paper is a paradigm shift from traditional biology to precision nanomedicine engineering using colloidal surface chemistry, biointerface dynamics, and translational manufacturing. We bridge material science with renal pathophysiology to develop a rational roadmap for future clinically available EV therapeutics targeting multifactorial renal fibrotic diseases.