# Therapeutic Potential of Extracellular Vesicles: From Biogenesis, Isolation and Molecular Characterization to Addressing Translational Gaps and Regulatory Barriers **Authors:** Dragan Primorac, Petar Brlek, Luka Bulić, Nenad Hrvatin, Vedrana Škaro, Petar Projić, Martina Glavan, Ijeoma Oleru, Pierre Rocheteau, Carlo Tremolada, Ariana DeMers, Mary A. Ambach, Don Buford, Tamara Knežević, Dimitrios Kouroupis, Cole Conforti, D. Wood Kimbrough, R. Peter Schnorr, Lindsay Williams, Raminta Vaiciuleviciute, Žan Fortuna, Lara Oprešnik, Blaž Curk, Miomir Knežević, Gordana Kalan Živčec, Adelina Hrkać, Dimitrios Tsoukas, Ilona Uzieliene, Jolita Pachaleva, Eiva Bernotiene, Kristiana Barbato, Neep Patel, Isabella Demirdjian Guanche, Evangelos V. Badiavas, Jana Mešić, Ana Medić Flajšman, Romina Milanič, Danijela Klarić, Vasiliki E. Kalodimou, Massimo Allegri, Johannes Brachmann, Wei Seong Toh, Nancy Duarte Delgado, Ali Mobasheri PMC · DOI: 10.3390/ijms27041676 · International Journal of Molecular Sciences · 2026-02-09 ## TL;DR This review explores how extracellular vesicles can be used for diagnosing and treating diseases, focusing on their biology, isolation methods, and regulatory challenges. ## Contribution The paper integrates molecular mechanisms with clinical applications to highlight the translational potential of extracellular vesicles in precision medicine. ## Key findings - EVs play a key role in intercellular communication and reflect the health status of their parent cells. - MSC-EVs show promise in regenerative medicine and cancer therapy. - Translational challenges include standardization, scalability, and regulatory validation. ## Abstract Extracellular vesicles (EVs) have emerged as essential mediators of intercellular communication, transporting a complex repertoire of lipids, proteins, and nucleic acids that mirror the physiological and pathological status of their parent cells. This review provides a comprehensive overview of EVs from their biogenesis and molecular composition to their translational potential in human disease. This review outlines the major classes of EVs, including exosomes, microvesicles, apoptotic bodies, and oncosomes, together with recent developments in their isolation, molecular characterization, and omics-based profiling. Special focus is given to the role of EVs in viral infection, inflammation, and immune regulation, as well as their contribution to disease development and cancer biology. Moreover, we highlight the emerging clinical applications of mesenchymal stem cell-derived EVs (MSC-EVs) in regenerative medicine and oncology, alongside the therapeutic modulation of EV signaling by photobiomodulation (PBM). Finally, we address key translational challenges related to standardization, scalability, and regulatory validation. As exosome-based therapeutics fall under strict FDA and EMA oversight, their translation further depends on harmonized quality controls and robust safety evaluation. By integrating molecular mechanisms with clinical applications, this review emphasizes the transformative potential of EVs as next-generation diagnostic and therapeutic tools in precision medicine. ## Linked entities - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** ARHGEF2 (Rho/Rac guanine nucleotide exchange factor 2) [NCBI Gene 9181] {aka GEF, GEF-H1, GEFH1, LFP40, Lfc, NEDMHM}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, FLI1 (Fli-1 proto-oncogene, ETS transcription factor) [NCBI Gene 2313] {aka BDPLT21, EWSR2, FLI-1, SIC-1}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, ABCA1 (ATP binding cassette subfamily A member 1) [NCBI Gene 19] {aka ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1}, CDX2 (caudal type homeobox 2) [NCBI Gene 1045] {aka CDX-3, CDX2/AS, CDX3}, HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1) [NCBI Gene 3181] {aka HNRNPA2, HNRNPB1, HNRPA2, HNRPA2B1, HNRPB1, IBMPFD2}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, CEACAM5 (CEA cell adhesion molecule 5) [NCBI Gene 1048] {aka CD66e, CEA}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, MMP14 (matrix metallopeptidase 14) [NCBI Gene 4323] {aka MMP-14, MMP-X1, MT-MMP, MT-MMP 1, MT1-MMP, MT1MMP}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, CDK9 (cyclin dependent kinase 9) [NCBI Gene 1025] {aka C-2k, CDC2L4, CTK1, PITALRE, TAK}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161] {aka CASC7, EIF2C2, LESKRES, LINC00980, PPD, Q10}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CD209 (CD209 molecule) [NCBI Gene 30835] {aka CDSIGN, CLEC4L, DC-SIGN, DC-SIGN1, hDC-SIGN}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MIR135B (microRNA 135b) [NCBI Gene 442891] {aka MIRN135B, mir-135b}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, YBX1 (Y-box binding protein 1) [NCBI Gene 4904] {aka BP-8, CBF-A, CSDA2, CSDB, DBPB, EFI-A}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, MIR192 (microRNA 192) [NCBI Gene 406967] {aka MIRN192, miR-192, miRNA192}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, MIR122 (microRNA 122) [NCBI Gene 406906] {aka MIR122A, MIRN122, MIRN122A, hsa-mir-122, miRNA122, miRNA122A}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CBL (Cbl proto-oncogene) [NCBI Gene 867] {aka C-CBL, CBL2, FRA11B, NSLL, RNF55}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, MPO (myeloperoxidase) [NCBI Gene 4353], RAB27A (RAB27A, member RAS oncogene family) [NCBI Gene 618035], CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, BST2 (bone marrow stromal cell antigen 2) [NCBI Gene 684] {aka CD317, HM1.24, TETHERIN} - **Diseases:** neuroinflammation (MESH:D000090862), atrophy (MESH:D001284), HBV infection (MESH:D006509), asthma (MESH:D001249), preeclampsia (MESH:D011225), acute lung injury (MESH:D055371), Cancer (MESH:D009369), diabetes (MESH:D003920), lung diseases (MESH:D008171), SIRS (MESH:D018746), skeletal disorders (MESH:C564967), fibrosarcoma (MESH:D005354), Alzheimer's (MESH:D000544), pancreatic cancer (MESH:D010190), Parkinson's (MESH:D010300), respiratory diseases (MESH:D012140), physical disability (MESH:D059445), fetal growth restriction (MESH:D005317), metabolic syndrome (MESH:D024821), prostate cancer (MESH:D011471), glioma (MESH:D005910), fibrosis (MESH:D005355), melanoma (MESH:D008545), osteosarcoma (MESH:D012516), sarcopenia (MESH:D055948), Inflammation (MESH:D007249), PDAC (MESH:D021441), diseases (MESH:D004194), degenerative disease (MESH:D019636), Injury (MESH:D014947), hypoxia (MESH:D000860), cartilage degeneration (MESH:D002357), SLE (MESH:D008180), laryngeal squamous cell carcinoma (MESH:D000077195), osteoarthritis (MESH:D010003), metabolic (MESH:D008659), neurological disorders (MESH:D009461), dysregulation (MESH:D021081), oral cancer (MESH:D009062), pneumonia (MESH:D011014), acute kidney injury (MESH:D058186), retinopathy (MESH:D058437), COPD (MESH:D029424), cardiomyopathy (MESH:D009202), hypoxic (MESH:D002534), neurological disease (MESH:D020271), lung adenocarcinoma (MESH:D000077192), prion diseases (MESH:D017096), organ dysfunction (MESH:D009102), autoimmune conditions (MESH:D001327), GDM (MESH:D016640), Ewing sarcoma (MESH:D012512), osteoporosis (MESH:D010024), toxicity (MESH:D064420), bone loss (MESH:D001847), knee osteoarthritis (MESH:D020370), psychosis (MESH:D011618), sarcoidosis (MESH:D012507), immunologic dysregulation (MESH:D007154), COVID-19 (MESH:D000086382) - **Chemicals:** lipoteichoic acids (MESH:C009900), agar (MESH:D000362), oxygen (MESH:D010100), acids (MESH:D000143), Ceramide (MESH:D002518), lipid A (MESH:D008050), cholesterol (MESH:D002784), DEXs (MESH:D003915), phospholipids (MESH:D010743), phosphatidylserine (MESH:D010718), HCT (MESH:D006852), SMs (MESH:D013109), OMV (-), ROS (MESH:D017382), sphingolipids (MESH:D013107), lipid (MESH:D008055), LPS (MESH:D008070), ATP (MESH:D000255) - **Species:** Pseudomonas aeruginosa (species) [taxon 287], Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562], Bifidobacterium longum (species) [taxon 216816], Human immunodeficiency virus 1 (no rank) [taxon 11676], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Salmonella enterica (species) [taxon 28901], Homo sapiens (human, species) [taxon 9606], Tannerella forsythia (species) [taxon 28112], Proteus mirabilis (species) [taxon 584], Staphylococcus aureus (species) [taxon 1280], Helicobacter pylori (species) [taxon 210], Neisseria meningitidis (species) [taxon 487], Akkermansia muciniphila (species) [taxon 239935], Lactiplantibacillus plantarum (species) [taxon 1590], Legionella pneumophila (species) [taxon 446], Gallus gallus (bantam, species) [taxon 9031], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Shigella (genus) [taxon 620] - **Cell lines:** MB49 — Mus musculus (Mouse), Mouse bladder transitional cell carcinoma, Cancer cell line (CVCL_7076), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), EMT6 tumors — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_1923), MC38 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_B288) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12940701/full.md ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940701/full.md ## References 257 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940701/full.md --- Source: https://tomesphere.com/paper/PMC12940701