{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:00:21Z","timestamp":1792522821520,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered <jats:italic>in vitro<\/jats:italic> and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. <jats:italic>In vitro<\/jats:italic>, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. <jats:italic>In vivo<\/jats:italic>, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.<\/jats:p>","DOI":"10.3389\/ebm.2024.10295","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T04:11:12Z","timestamp":1732075872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Engineering ADSCs by manipulating YAP for lymphedema treatment in a mouse tail 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