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Animals were randomized into four groups: Control, ALE only, VLNT only, and VLNT combined with ALE (VLNT\u2009+\u2009ALE). ALE was prepared using a mechanical emulsification and filtration protocol. Edema resolution was monitored by limb circumference. Lymphatic drainage function was visualized via indocyanine green (ICG) lymphography. Histological assessments included Masson\u2019s trichrome and immunofluorescence for LYVE-1 (lymphangiogenesis), CD31 (angiogenesis), and MECA-79 (high endothelial venules, HEVs) to evaluate structural and functional regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The VLNT\u2009+\u2009ALE group achieved the most rapid and significant edema regression compared to VLNT or ALE alone. ICG lymphography revealed that the combined therapy orchestrated the formation of continuous, linear lymphatic channels, effectively eliminating dermal backflow. Histologically, ALE treatment significantly increased the density of both LYVE-1\n                      <jats:sup>+<\/jats:sup>\n                      lymphatic vessels and CD31\n                      <jats:sup>+<\/jats:sup>\n                      blood vessels, suggesting a dual-regenerative effect on the microenvironment. ALE directly promoted tube formation in human lymphatic endothelial cells (HLECs), confirming its pro-lymphangiogenic activity in vitro. Crucially, within the transplanted lymph nodes, ALE treatment restored the expression of MECA-79\n                      <jats:sup>+<\/jats:sup>\n                      HEVs to levels comparable to healthy young nodes. This indicates that ALE not only supports graft survival but also preserves the essential lymphoid microarchitecture required for immune surveillance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cell-free ALE synergistically enhances the therapeutic efficacy of VLNT by promoting vascular-lymphatic coupling and restoring the functional immune niche of transplanted nodes. As a readily available, safe, and cell-free biologic adjuvant, ALE represents a promising translational strategy to optimize surgical outcomes in secondary lymphedema.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13770-026-00829-x","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:34:10Z","timestamp":1784612050000},"page":"1101-1114","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell-Free Adipose Liquid Extract Combined with Vascularized Lymph Node Transfer for Treating Lymphedema: Implications for Human Therapy"],"prefix":"10.1007","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-7549","authenticated-orcid":false,"given":"Lingli","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanhong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Chiarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria Dal","family":"Pr\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ubaldo","family":"Armato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"De Santis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shune","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-3245","authenticated-orcid":false,"given":"Chengliang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"829_CR1","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.jamcollsurg.2021.03.002","volume":"232","author":"MV Schaverien","year":"2021","unstructured":"Schaverien MV, Asaad M, Selber JC, Liu J, Chen DN, Hall MS, et al. 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Semin Immunol. 2008;20:109\u201316.","journal-title":"Semin Immunol"}],"container-title":["Tissue Engineering and Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-026-00829-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13770-026-00829-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-026-00829-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:04:37Z","timestamp":1790643877000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13770-026-00829-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["829"],"URL":"https:\/\/doi.org\/10.1007\/s13770-026-00829-x","relation":{},"ISSN":["1738-2696","2212-5469"],"issn-type":[{"value":"1738-2696","type":"print"},{"value":"2212-5469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"13 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors have no financial conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol involving human adipose tissue was approved by the Biomedical Research Ethics Committee of the Affiliated Hospital of Zunyi Medical University (IRB No. KLLY-2022-044; approval date 31 December 2022). Written informed consent was obtained from all donors prior to tissue collection. All procedures involving human participants were conducted in accordance with the Declaration of Helsinki. All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Zunyi Medical University (IACUC approval No. [2022]1-169; approval date 8 March 2022). The care and use of animals complied with the Guide for the Care and Use of Laboratory Animals (8th edition) and the ARRIVE 2.0 guidelines.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}