Therapeutic potential of lymphatic endothelial progenitor cells in secondary lymphedema: a preclinical murine study.

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dc.contributor.authorJaunarena Marin, Ibon
dc.contributor.authorIglesias Gaspar, Mayte
dc.contributor.authorArriola Riestra, Ignacio
dc.contributor.authorIzeta, Ander
dc.contributor.authorDiez Itza, Irene
dc.contributor.authorLekuona, Arantxa
dc.contributor.authorLafuente Echevarria, Hector
dc.date.accessioned2026-10-08T15:27:09Z
dc.date.available2026-10-08T15:27:09Z
dc.date.issued2026-08-01
dc.date.updated2026-10-08T15:27:09Z
dc.description.abstractBackground: Secondary lymphedema is a chronic complication of oncologic surgery and radiotherapy for which effective disease-modifying therapies remain lacking. While mesenchymal stem cells (MSCs) have shown partial benefit in experimental models, direct functional comparison with lineage-committed lymphatic endothelial progenitor cells (LEPCs) remains limited. Methods: Secondary lymphedema was induced in C57BL/6J mice by circumferential tail skin excision with disruption of superficial lymphatics. Animals received intradermal phosphate-buffered saline (PBS), MSCs, or adipose-derived LEPCs on postoperative days 1 and 7. Lymphatic function was longitudinally quantified using IVIS-based near-infrared indocyanine green (ICG) imaging with standardized region-of-interest analysis. Tail diameter was measured serially throughout follow-up as a complementary morphometric parameter. Tissue remodeling was assessed by Picrosirius Red staining and qualitative LYVE-1 immunofluorescence. Statistical analysis incorporated mixed-effects modeling to evaluate treatment group, sex, time, and their interaction terms, with estimation of effect sizes and 95% confidence intervals. Results: LEPC-treated mice demonstrated higher IVIS signal intensity than MSC- and PBS-treated animals, consistent with improved lymphatic transport at the injury site. Longitudinal tail diameter analysis showed a more favorable temporal profile in the LEPC group relative to controls, with exploratory analysis suggesting potential variations in temporal profiles between sexes that warrant further investigation in larger cohorts. Histologic analysis showed reduced non-tissue/void area and a more favorable qualitative pattern of LYVE-1 staining in LEPC-treated tissue. Conclusions: LEPC administration enhanced functional and structural recovery in a murine model of secondary lymphedema. These findings support further translational evaluation of LEPC-based approaches as a regenerative strategy for secondary lymphedema.en
dc.description.sponsorshipI.A.-A. was supported by a Predoctoral Fellowship for the Training of Non-Doctoral Research Personnel (PRE_2023_1_0119) from the Basque Government and by a donation from Fundación Jesús de Gangoiti Barrera (2022 and 2023). This work was supported in part by grants from the Instituto de Salud Carlos III (PI22/01247, CERT22/00032, RD24/0014/0012, DTS24/00167, PT23/00142), co-funded by the European Union, and by the Basque Government (KK-2024/00041, 2020111004), supporting the cell therapy research line. The experimental work was also supported through the continuation of the Bottom-Up research project promoted by the Department of Gynecology and Obstetrics of Donostia University Hospital/OSI Donostialdea, within the Basque Government Department of Health Bottom-Up programme. Dr. Ibon Jaunarena received protected research time through the 2022 Intensification Programme for Research Activity funded by the Colegio de Médicos de Gipuzkoa (INTBI022/001).en
dc.identifier.citationJaunarena, I., Iglesias-Gaspar, M.-T., Arriola-Alvarez, I., Izeta, A., Diez-Itza, I., Lekuona, A., & Lafuente, H. (2026). Therapeutic potential of lymphatic endothelial progenitor cells in secondary lymphedema: a preclinical murine study. Biomedicines, 14(8). https://doi.org/10.3390/BIOMEDICINES14081782
dc.identifier.doi10.3390/BIOMEDICINES14081782
dc.identifier.eissn2227-9059
dc.identifier.urihttps://hdl.handle.net/20.500.14454/6769
dc.language.isoeng
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)
dc.rightsCopyright: © 2026 by the authors
dc.subject.otherCell therapy
dc.subject.otherLymphangiogenesis
dc.subject.otherLymphatic endothelial progenitor cells
dc.subject.otherLymphatic regeneration
dc.subject.otherMouse tail lymphedema model
dc.subject.otherRegenerative medicine
dc.subject.otherSecondary lymphedema
dc.titleTherapeutic potential of lymphatic endothelial progenitor cells in secondary lymphedema: a preclinical murine study.en
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue8
oaire.citation.titleBiomedicines
oaire.citation.volume14
oaire.licenseConditionhttps://creativecommons.org/licenses/by/4.0/
oaire.versionVoR
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