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It has attracted considerable attention from researchers in regenerative medicine due to its structural robustness as a scaffold and its content of epithelial and mesenchymal stromal cells, which exhibit low immunogenicity and immunotoxicity while retaining stem cell potential. Moreover, hAM possesses a range of therapeutic properties relevant to the treatment of various diseased tissues. These effects are mediated by extracellular components, including secreted factors, matrix elements, and extracellular vesicles (EVs). Despite this, a detailed characterization of the extracellular vesicles fraction of hAM, particularly regarding its molecular content and functional properties, remains limited. In this minireview, we summarize the available literature with particular attention to ophthalmology. Recent studies suggest that hAM-derived EVs may provide neuroprotective, anti-inflammatory, and pro-regenerative effects, supporting tissue repair and homeostasis in ocular pathologies. Understanding the molecular cargo of these vesicles, including proteins, miRNAs, and signaling molecules, could help unlock their therapeutic potential and guide the development of standardized cell-free treatments. Taken together, hAM-derived EVs represent a compelling cell-free therapeutic platform for ophthalmology, recapitulating many of the beneficial actions of the native tissue. However, clinical translation requires overcoming critical hurdles. We highlight these unresolved challenges, including manufacturing standardization, potency assessment, and reproducibility, while outlining the key safety and regulatory considerations essential for future ocular therapies.<\/jats:p>","DOI":"10.1007\/s11033-026-12756-0","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:55:18Z","timestamp":1789736118000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activities of human amniotic membrane extracellular vesicles with a focus on ophthalmology"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-4094","authenticated-orcid":false,"given":"Matteo","family":"Lulli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6083-0380","authenticated-orcid":false,"given":"Sara","family":"Calcagno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Peppicelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Isoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-2974","authenticated-orcid":false,"given":"Indu-Pal","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Papucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Magnelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Mannini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Schiavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"12756_CR1","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1007\/s00441-012-1424-6","volume":"349","author":"AC Mamede","year":"2012","unstructured":"Mamede AC, Carvalho MJ, Abrantes AM, Laranjo M, Maia CJ, Botelho MF (2012) Amniotic membrane: from structure and functions to clinical applications. 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