{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:06:08Z","timestamp":1789470368175,"version":"build-2803163510"},"reference-count":121,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2509901"],"award-info":[{"award-number":["2023YFC2509901"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Age-related osteoporosis is characterized by the simultaneous loss of bone mass and the regression of CD31hiEmcnhi (Type H) vessels, a specialized capillary subtype that functionally couples angiogenesis with osteogenesis. The endothelial progenitor cell (EPC) compartment, comprising myeloid angiogenic cells (MACs) and endothelial colony-forming cells (ECFCs), contributes to the maintenance of this vascular niche; however, its regenerative potential declines with age, partly as a consequence of cellular senescence and acquisition of the senescence-associated secretory phenotype (SASP). Given the clinical hurdles of conventional cell transplantation, therapeutic development has shifted toward cell-free strategies based on the MAC\/ECFC secretome, particularly extracellular vesicles (EVs). In this review, we clarify the distinction between MACs and ECFCs to resolve historical conceptual ambiguities, and examine how their paracrine cues regulate angiogenic\u2013osteogenic coupling. We then synthesize current evidence on endothelial EV cargo and discuss how aging remodels vesicle composition and function to drive vascular\u2013bone uncoupling. Beyond existing reviews on EPC-EVs, Type H vessels, or EV-based bone regeneration, we add a protocol-driven re-annotation and explicitly distinguish bone-related studies methodologically compatible with MAC-derived EVs from adjacent evidence using other endothelial cell sources and mechanistic support from non-skeletal models. Finally, we compare bioengineering strategies, including preconditioning, precision cargo engineering, surface targeting, and scaffold\/hydrogel delivery, aimed at correcting senescence-associated cargo liabilities and improving translational readiness.<\/jats:p>","DOI":"10.3390\/ijms27188202","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:32:01Z","timestamp":1789468321000},"page":"8202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reprogramming the Aging Type H Vascular Niche via Myeloid Angiogenic Cell-Derived Extracellular Vesicles: Mechanisms, Engineering Strategies, and Translational Perspectives"],"prefix":"10.3390","volume":"27","author":[{"given":"Jinxin","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing 100044, China"},{"name":"Department of Trauma and Orthopedics, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing 100044, China"},{"name":"Department of Trauma and Orthopedics, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trauma and Neural Regeneration, Ministry of Education, Peking University, Beijing 100044, China"},{"name":"National Center for Trauma Medicine, Beijing 100044, China"},{"name":"Department of Central Laboratory and Institute of Clinical Molecular Biology, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The Global Prevalence of Osteoporosis in the World: A Comprehensive Systematic Review and Meta-Analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J. 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