References
-
Sleigh, B. C. & Manna, B. In: StatPearls (StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC., 2023).
-
Brown, S., Dayan, J. H., Kataru, R. P. & Mehrara, B. J. The vicious circle of stasis, inflammation, and fibrosis in lymphedema. Plast. Reconstr. Surg. 151, 330e–341e. https://doi.org/10.1097/prs.0000000000009866 (2023).
-
Grada, A. A. & Phillips, T. J. Lymphedema: Pathophysiology and clinical manifestations. J. Am. Acad. Dermatol. 77, 1009–1020. https://doi.org/10.1016/j.jaad.2017.03.022 (2017).
-
Jia, L. et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: A cross-sectional study. Lancet. Public health 5, e661–e671. https://doi.org/10.1016/s2468-2667(20)30185-7 (2020).
-
Thompson, B., Gaitatzis, K., de Janse Jonge, X., Blackwell, R. & Koelmeyer, L. A. Manual lymphatic drainage treatment for lymphedema: A systematic review of the literature. J. Cancer Survivorship Res. Practice 15, 244–258. https://doi.org/10.1007/s11764-020-00928-1 (2021).
-
Rafn, B. S. et al. Examining the efficacy of treatments for arm lymphedema in breast cancer survivors: An overview of systematic reviews with meta-analyses. EClinicalMedicine 67, 102397. https://doi.org/10.1016/j.eclinm.2023.102397 (2024).
-
Cheng, G. et al. Clinical application of magnetic resonance lymphangiography in the vascularized omental lymph nodes transfer with or without lymphaticovenous anastomosis for cancer-related lower extremity lymphedema. Quant. Imaging Med. Surg. 13, 5945–5957. https://doi.org/10.21037/qims-22-1443 (2023).
-
Shah, C., Asha, W. & Vicini, F. Current diagnostic tools for breast cancer-related lymphedema. Curr. Oncol. Rep. 25, 151–154. https://doi.org/10.1007/s11912-023-01357-w (2023).
-
Itoh, F. & Watabe, T. TGF-β signaling in lymphatic vascular vessel formation and maintenance. Front. Physiol. 13, 1081376. https://doi.org/10.3389/fphys.2022.1081376 (2022).
-
Sano, M. et al. Potential role of transforming growth factor-beta 1/Smad signaling in secondary lymphedema after cancer surgery. Cancer Sci. 111, 2620–2634. https://doi.org/10.1111/cas.14457 (2020).
-
Brown, S. et al. Topical captopril: A promising treatment for secondary lymphedema. Transl. Res. J. Lab. Clin. Med. 257, 43–53. https://doi.org/10.1016/j.trsl.2023.01.005 (2023).
-
Shimizu, Y., Che, Y. & Murohara, T. Therapeutic lymphangiogenesis is a promising strategy for secondary lymphedema. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24097774 (2023).
-
Alderfer, L., Russo, E., Archilla, A., Coe, B. & Hanjaya-Putra, D. Matrix stiffness primes lymphatic tube formation directed by vascular endothelial growth factor-C. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 35, e21498. https://doi.org/10.1096/fj.202002426RR (2021).
-
Ehyaeeghodraty, V. et al. Effects of mobilized peripheral blood stem cells on treatment of primary lower extremity lymphedema. J. Vasc. Surg. Venous Lymphat. Disord. 8, 445–451. https://doi.org/10.1016/j.jvsv.2019.10.019 (2020).
-
Schaverien, M. V. & Aldrich, M. B. New and emerging treatments for lymphedema. Semin. Plast. Surg. 32, 48–52. https://doi.org/10.1055/s-0038-1632403 (2018).
-
Mahé, P. et al. Automatic identification of mixed bacterial species fingerprints in a MALDI-TOF mass-spectrum. Bioinformatics 30, 1280–1286. https://doi.org/10.1093/bioinformatics/btu022 (2014).
-
Hu, L. R. & Pan, J. Adipose-derived stem cell therapy shows promising results for secondary lymphedema. World J. Stem Cells 12, 612–620. https://doi.org/10.4252/wjsc.v12.i7.612 (2020).
-
Qian, H. et al. Cancer stemness and metastatic potential of the novel tumor cell line K3: An inner mutated cell of bone marrow-derived mesenchymal stem cells. Oncotarget 8, 39522–39533. https://doi.org/10.18632/oncotarget.17133 (2017).
-
Sun, Z. et al. The role and mechanism of miR-374 regulating the malignant transformation of mesenchymal stem cells. Am. J. Transl. Res. 10, 3224–3232 (2018).
-
Ren, Y. & Zhang, H. Emerging role of exosomes in vascular diseases. Front. Cardiovasc. Med. 10, 1090909. https://doi.org/10.3389/fcvm.2023.1090909 (2023).
-
Chen, H. et al. Exosomes, a new star for targeted delivery. Front. Cell Dev. Biol. 9, 751079. https://doi.org/10.3389/fcell.2021.751079 (2021).
-
An, Y. et al. Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolif. 54, e12993. https://doi.org/10.1111/cpr.12993 (2021).
-
Shen, K. et al. Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages. Free Radical Biol. Med. 165, 54–66. https://doi.org/10.1016/j.freeradbiomed.2021.01.023 (2021).
-
Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science https://doi.org/10.1126/science.aau6977 (2020).
-
Li, B. et al. Delivery of vascular endothelial growth factor (VEGFC) via engineered exosomes improves lymphedema. Ann. Transl. Med. 8, 1498. https://doi.org/10.21037/atm-20-6605 (2020).
-
Ting, Z. et al. Exosomes derived from human umbilical cord Wharton’s jelly mesenchymal stem cells ameliorate experimental lymphedema. Clin. Transl. Med. 11, e384. https://doi.org/10.1002/ctm2.384 (2021).
-
Choi, S. H. et al. Oral transforming growth factor-beta receptor 1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity. Cancer Commun. 44, 884–888. https://doi.org/10.1002/cac2.12589 (2024).
-
Park, S. A. et al. EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling. Cell. Mol. Life Sci. CMLS 72, 2023–2039. https://doi.org/10.1007/s00018-014-1798-6 (2015).
-
Yoon, S. H. et al. EW-7197, a transforming growth factor-beta type I receptor kinase inhibitor, ameliorates acquired lymphedema in a mouse tail model. Lymphat. Res. Biol. 18, 433–438. https://doi.org/10.1089/lrb.2018.0070 (2020).
-
Alasmari, W. A. et al. Molecular and cellular mechanisms involved in adipose-derived stem cell and their extracellular vesicles in an experimental model of cardio- renal syndrome type 3: Histological and biochemical study. Tissue Cell 77, 101842. https://doi.org/10.1016/j.tice.2022.101842 (2022).
-
Yang, X. X., Sun, C., Wang, L. & Guo, X. L. New insight into isolation, identification techniques and medical applications of exosomes. J. Control. Release Off. J. Control. Release Soc. 308, 119–129. https://doi.org/10.1016/j.jconrel.2019.07.021 (2019).
-
Liang, Y. et al. Adipose mesenchymal stromal cell-derived exosomes carrying MiR-122–5p antagonize the inhibitory effect of dihydrotestosterone on hair follicles by targeting the TGF-β1/SMAD3 signaling pathway. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24065703 (2023).
-
Yang, G. et al. Circ-CSPP1 knockdown suppresses hepatocellular carcinoma progression through miR-493-5p releasing-mediated HMGB1 downregulation. Cell. Signal. 86, 110065. https://doi.org/10.1016/j.cellsig.2021.110065 (2021).
-
Wei, W. F. et al. Cancer-associated fibroblast-derived PAI-1 promotes lymphatic metastasis via the induction of EndoMT in lymphatic endothelial cells. J. Exp. Clin. Cancer Res. CR 42, 160. https://doi.org/10.1186/s13046-023-02714-0 (2023).
-
Nikolaev, V. V. et al. An evaluation of lymphedema using optical coherence tomography: A rat limb model approach. Diagnostics https://doi.org/10.3390/diagnostics13172822 (2023).
-
Harb, A. A. et al. Creation of a rat lower limb lymphedema model. Ann. Plast. Surg. 85, S129-s134. https://doi.org/10.1097/sap.0000000000002323 (2020).
-
Yang, C. Y. et al. Developing a lower limb lymphedema animal model with combined lymphadenectomy and low-dose radiation. Plast. Reconstr. Surg. Glob. Open 2, e121. https://doi.org/10.1097/gox.0000000000000064 (2014).
-
Ahmed, S. et al. Murine hindlimb lymphedema model: optimization and evaluation of radiation. Breast Cancer Res. BCR 27, 168. https://doi.org/10.1186/s13058-025-02112-8 (2025).
-
Hadrian, R. & Palmes, D. Animal models of secondary lymphedema: New approaches in the search for therapeutic options. Lymphat. Res. Biol. 15, 2–16. https://doi.org/10.1089/lrb.2016.0015 (2017).
-
Khan, N. et al. Effects of diet-induced obesity in the development of lymphedema in the animal model: A literature review. Obes. Res. Clin. Pract. 16, 197–205. https://doi.org/10.1016/j.orcp.2022.05.003 (2022).
-
Morita, Y. et al. Establishment of a simple, reproducible, and long-lasting hind limb animal model of lymphedema. Plast. Reconstr. Surg. Glob. Open 11, e5243. https://doi.org/10.1097/gox.0000000000005243 (2023).
-
Hayashida, K. et al. Adipose-derived stem cells and vascularized lymph node transfers successfully treat mouse hindlimb secondary lymphedema by early reconnection of the lymphatic system and lymphangiogenesis. Plast. Reconstr. Surg. 139, 639–651. https://doi.org/10.1097/prs.0000000000003110 (2017).
-
Stuckey, J. E., Makhija, S. D., Reimer, D. C. & Eswaraka, J. R. Effects of different grades of carbon dioxide on euthanasia of mice (Mus musculus). J. Am. Assoc. Lab. Animal Sci. JAALAS 62, 430–437. https://doi.org/10.30802/aalas-jaalas-23-000023 (2023).
-
Ruliffson, B. N. K. & Whittington, C. F. Regulating lymphatic vasculature in fibrosis: Understanding the biology to improve the modeling. Adv. Biol. https://doi.org/10.1002/adbi.202200158 (2023).
-
Brix, B. et al. Biology of Lymphedema. Biology https://doi.org/10.3390/biology10040261 (2021).
-
Duhon, B. H., Phan, T. T., Taylor, S. L., Crescenzi, R. L. & Rutkowski, J. M. Current mechanistic understandings of lymphedema and lipedema: Tales of fluid, fat, and fibrosis. Int. J. Mol. Sci. https://doi.org/10.3390/ijms23126621 (2022).
-
Nelson, T. S. et al. Lymphatic remodelling in response to lymphatic injury in the hind limbs of sheep. Nat. Biomed. Eng. 4, 649–661. https://doi.org/10.1038/s41551-019-0493-1 (2020).
-
Zhou, H., Wang, M., Hou, C., Jin, X. & Wu, X. Exogenous VEGF-C augments the efficacy of therapeutic lymphangiogenesis induced by allogenic bone marrow stromal cells in a rabbit model of limb secondary lymphedema. Jpn. J. Clin. Oncol. 41, 841–846. https://doi.org/10.1093/jjco/hyr055 (2011).
-
Wu, G. et al. Rhesus monkey is a new model of secondary lymphedema in the upper limb. Int. J. Clin. Exp. Pathol. 7, 5665–5673 (2014).
-
Hadamitzky, C. & Pabst, R. Acquired lymphedema: An urgent need for adequate animal models. Can. Res. 68, 343–345. https://doi.org/10.1158/0008-5472.Can-07-2454 (2008).
-
Campos, J. L. et al. Popliteal vascular lymph node resection in the rabbit hindlimb for secondary lymphedema induction. J. Visual. Exp. JoVE https://doi.org/10.3791/64576 (2022).
-
Hong, P., Yang, H., Wu, Y., Li, K. & Tang, Z. The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: A comprehensive review. Stem Cell Res. Ther. 10, 242. https://doi.org/10.1186/s13287-019-1358-y (2019).
-
Lotfy, A., AboQuella, N. M. & Wang, H. Mesenchymal stromal/stem cell (MSC)-derived exosomes in clinical trials. Stem Cell Res. Ther. 14, 66. https://doi.org/10.1186/s13287-023-03287-7 (2023).
-
Erratum to delivery of vascular endothelial growth factor (VEGFC) via engineered exosomes improves lymphedema. Ann. Transl. Med. 9, 1281, https://doi.org/10.21037/atm-2021-22 (2021).
-
Lu, J. H. et al. A novel dressing composed of adipose stem cells and decellularized Wharton’s Jelly facilitated wound healing and relieved lymphedema by enhancing angiogenesis and lymphangiogenesis in a rat model. J. Funct. Biomater. https://doi.org/10.3390/jfb14020104 (2023).
-
Baik, J. E. et al. TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation. Clin. Transl. Med. 12, e758. https://doi.org/10.1002/ctm2.758 (2022).
-
Liao, X. et al. LncRNA-Gm9866 promotes liver fibrosis by activating TGFβ/Smad signaling via targeting Fam98b. J. Transl. Med. 21, 778. https://doi.org/10.1186/s12967-023-04642-1 (2023).
-
Zhao, X. et al. Penetration cascade of size switchable nanosystem in desmoplastic stroma for improved pancreatic cancer therapy. ACS Nano 15, 14149–14161. https://doi.org/10.1021/acsnano.0c08860 (2021).
-
Chen, J. et al. TGF-β1-induced SOX18 elevation promotes hepatocellular carcinoma progression and metastasis through transcriptionally upregulating PD-L1 and CXCL12. Gastroenterology 167, 264–280. https://doi.org/10.1053/j.gastro.2024.02.025 (2024).
-
Wang, X., Wang, H., Cao, J. & Ye, C. Exosomes from adipose-derived stem cells promotes VEGF-C-dependent lymphangiogenesis by regulating miRNA-132/TGF-β pathway. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 49, 160–171. https://doi.org/10.1159/000492851 (2018).
-
Qian, L., Pi, L., Fang, B. R. & Meng, X. X. Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis. Lab. Investig. J. Tech. Methods Pathol. 101, 1254–1266. https://doi.org/10.1038/s41374-021-00611-8 (2021).
-
Kumar, V. A. et al. Treatment of hind limb ischemia using angiogenic peptide nanofibers. Biomaterials 98, 113–119. https://doi.org/10.1016/j.biomaterials.2016.04.032 (2016).
-
Alderfer, L., Hall, E. & Hanjaya-Putra, D. Harnessing biomaterials for lymphatic system modulation. Acta Biomater. 133, 34–45. https://doi.org/10.1016/j.actbio.2021.06.006 (2021).
