Abstract
Lymphatic vasculature plays essential role in interstitial tissue uptake, immune cell transport and dietary lipid absorption. Increasing evidence has demonstrated the contribution of lymphangiogenesis to tissue repair and regeneration, which is associated with multiple factors such as improved tissue homeostasis, inflammation resolution, and immunomodulation effects. Meanwhile, lymphangiogenesis has the potential to regulate cell growth and proliferation through paracrine effects. Lymphatic vessels can also be important components of the stem cell niche and participate in regulating stem cell quiescency or activity. In perspective, the functions and mechanisms of lymphatic vessels in tissue repair and regeneration deserve further investigation. Novel strategies to stimulate lymphangiogenesis by using pharmacological, genetic, and lymphatic tissue engineering will be prospective to promote tissue repair and regeneration.
Keywords: Lymphatic vessels, tissue repair and regeneration, tissue homeostasis, immunomodulation, proliferation, stem cell niche.
[1]
Petrova TV, Koh GY. Biological functions of lymphatic vessels. Science 2020; 369(6500): eaax4063.
[http://dx.doi.org/10.1126/science.aax4063] [PMID: 32646971]
[http://dx.doi.org/10.1126/science.aax4063] [PMID: 32646971]
[2]
Hu X, Deng Q, Ma L, et al. Meningeal lymphatic vessels regulate brain tumor drainage and immunity. Cell Res 2020; 30(3): 229-43.
[http://dx.doi.org/10.1038/s41422-020-0287-8] [PMID: 32094452]
[http://dx.doi.org/10.1038/s41422-020-0287-8] [PMID: 32094452]
[3]
Oliver G, Kipnis J, Randolph GJ, Harvey NL. The lymphatic vasculature in the 21st century: Novel functional roles in homeostasis and disease. Cell 2020; 182(2): 270-96.
[http://dx.doi.org/10.1016/j.cell.2020.06.039] [PMID: 32707093]
[http://dx.doi.org/10.1016/j.cell.2020.06.039] [PMID: 32707093]
[4]
Stritt S, Koltowska K, Mäkinen T. Homeostatic maintenance of the lymphatic vasculature. Trends Mol Med 2021; 27(10): 955-70.
[http://dx.doi.org/10.1016/j.molmed.2021.07.003] [PMID: 34332911]
[http://dx.doi.org/10.1016/j.molmed.2021.07.003] [PMID: 34332911]
[5]
Ogino R, Hayashida K, Yamakawa S, Morita E. Adipose-Derived stem cells promote intussusceptive lymphangiogenesis by restricting dermal fibrosis in irradiated tissue of mice. Int J Mol Sci 2020; 21(11): E3885.
[http://dx.doi.org/10.3390/ijms21113885] [PMID: 32485955]
[http://dx.doi.org/10.3390/ijms21113885] [PMID: 32485955]
[6]
Henri O, Pouehe C, Houssari M, et al. Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation 2016; 133(15): 1484-97.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020143] [PMID: 26933083]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.020143] [PMID: 26933083]
[7]
Oka M, Iwata C, Suzuki HI, et al. Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. Blood 2008; 111(9): 4571-9.
[http://dx.doi.org/10.1182/blood-2007-10-120337] [PMID: 18310502]
[http://dx.doi.org/10.1182/blood-2007-10-120337] [PMID: 18310502]
[8]
Kinashi H, Ito Y, Sun T, Katsuno T, Takei Y. Roles of the TGF-β−VEGF-C pathway in fibrosis-related lymphangiogenesis. Int J Mol Sci 2018; 19(9): E2487.
[http://dx.doi.org/10.3390/ijms19092487] [PMID: 30142879]
[http://dx.doi.org/10.3390/ijms19092487] [PMID: 30142879]
[9]
Takeda A, Hollmén M, Dermadi D, et al. Single-Cell survey of human lymphatics unveils marked endothelial cell heterogeneity and mechanisms of homing for neutrophils. Immunity 2019; 51(3): 561-572.e5.
[http://dx.doi.org/10.1016/j.immuni.2019.06.027] [PMID: 31402260]
[http://dx.doi.org/10.1016/j.immuni.2019.06.027] [PMID: 31402260]
[10]
Rademakers T, van der Vorst EP, Daissormont IT, et al. Adventitial lymphatic capillary expansion impacts on plaque T cell accumulation in atherosclerosis. Sci Rep 2017; 7: 45263.
[http://dx.doi.org/10.1038/srep45263] [PMID: 28349940]
[http://dx.doi.org/10.1038/srep45263] [PMID: 28349940]
[11]
Vieira JM, Norman S, Villa Del Campo C, et al. The cardiac lymphatic system stimulates resolution of inflammation following myocardial infarction. J Clin Invest 2018; 128(8): 3402-12.
[http://dx.doi.org/10.1172/JCI97192] [PMID: 29985167]
[http://dx.doi.org/10.1172/JCI97192] [PMID: 29985167]
[12]
Yoon SY, Dieterich LC, Karaman S, et al. An important role of cutaneous lymphatic vessels in coordinating and promoting anagen hair follicle growth. PLoS One 2019; 14(7): e0220341.
[http://dx.doi.org/10.1371/journal.pone.0220341] [PMID: 31344105]
[http://dx.doi.org/10.1371/journal.pone.0220341] [PMID: 31344105]
[13]
Liu X, De la Cruz E, Gu X, et al. Lymphoangiocrine signals promote cardiac growth and repair. Nature 2020; 588(7839): 705-11.
[http://dx.doi.org/10.1038/s41586-020-2998-x] [PMID: 33299187]
[http://dx.doi.org/10.1038/s41586-020-2998-x] [PMID: 33299187]
[14]
Bei Y, Huang Z, Feng X, et al. Lymphangiogenesis contributes to exercise-induced physiological cardiac growth. J Sport Health Sci 2022; S2095-2546(22): 00037-0.
[http://dx.doi.org/10.1016/j.jshs.2022.02.005] [PMID: 35218948]
[http://dx.doi.org/10.1016/j.jshs.2022.02.005] [PMID: 35218948]
[15]
Hill JA. Braking bad hypertrophy. N Engl J Med 2015; 372(22): 2160-2.
[http://dx.doi.org/10.1056/NEJMcibr1504187] [PMID: 26017827]
[http://dx.doi.org/10.1056/NEJMcibr1504187] [PMID: 26017827]
[16]
Gao R, Wang L, Bei Y, et al. Long Noncoding RNA cardiac physiological hypertrophy-associated regulator induces cardiac physiological hypertrophy and promotes functional recovery after myocardial ischemia-reperfusion injury. Circulation 2021; 144(4): 303-17.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050446] [PMID: 34015936]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050446] [PMID: 34015936]
[17]
Gur-Cohen S, Yang H, Baksh SC, et al. Stem cell-driven lymphatic remodeling coordinates tissue regeneration. Science 2019; 366(6470): 1218-25.
[http://dx.doi.org/10.1126/science.aay4509] [PMID: 31672914]
[http://dx.doi.org/10.1126/science.aay4509] [PMID: 31672914]
[18]
Schaupper M, Jeltsch M, Rohringer S, Redl H, Holnthoner W. Lymphatic vessels in regenerative medicine and tissue engineering. Tissue Eng Part B Rev 2016; 22(5): 395-407.
[http://dx.doi.org/10.1089/ten.teb.2016.0034] [PMID: 27142568]
[http://dx.doi.org/10.1089/ten.teb.2016.0034] [PMID: 27142568]
[19]
Saaristo A, Tammela T, Farkkilā A, et al. Vascular endothelial growth factor-C accelerates diabetic wound healing. Am J Pathol 2006; 169(3): 1080-7.
[http://dx.doi.org/10.2353/ajpath.2006.051251] [PMID: 16936280]
[http://dx.doi.org/10.2353/ajpath.2006.051251] [PMID: 16936280]
[20]
Hamada T, Hidaka M, Takatsuki M, et al. The relationship between lymphangiogenesis and liver regeneration after partial hepatectomy in cholestatic mice. Lymphat Res Biol 2020; 18(4): 322-8.
[http://dx.doi.org/10.1089/lrb.2019.0068] [PMID: 32069131]
[http://dx.doi.org/10.1089/lrb.2019.0068] [PMID: 32069131]
[21]
Nakamoto S, Ito Y, Nishizawa N, et al. Lymphangiogenesis and accumulation of reparative macrophages contribute to liver repair after hepatic ischemia-reperfusion injury. Angiogenesis 2020; 23(3): 395-410.
[http://dx.doi.org/10.1007/s10456-020-09718-w] [PMID: 32162023]
[http://dx.doi.org/10.1007/s10456-020-09718-w] [PMID: 32162023]
[22]
Vivien CJ, Pichol-Thievend C, Sim CB, et al. Vegfc/d-dependent regulation of the lymphatic vasculature during cardiac regeneration is influenced by injury context. NPJ Regen Med 2019; 4: 18.
[http://dx.doi.org/10.1038/s41536-019-0079-2] [PMID: 31452940]
[http://dx.doi.org/10.1038/s41536-019-0079-2] [PMID: 31452940]
[23]
Feng X, Travisano S, Pearson CA, Lien CL, Harrison MRM. The lymphatic system in zebrafish heart development, regeneration and disease modeling. J Cardiovasc Dev Dis 2021; 8(2): 21.
[http://dx.doi.org/10.3390/jcdd8020021] [PMID: 33669620]
[http://dx.doi.org/10.3390/jcdd8020021] [PMID: 33669620]
[24]
Lin QY, Zhang YL, Bai J, Liu JQ, Li HH. VEGF-C/VEGFR-3 axis protects against pressure-overload induced cardiac dysfunction through regulation of lymphangiogenesis. Clin Transl Med 2021; 11(3): e374.
[http://dx.doi.org/10.1002/ctm2.374] [PMID: 33783987]
[http://dx.doi.org/10.1002/ctm2.374] [PMID: 33783987]
[25]
Qiu Y, Pan X, Chen Y, Xiao J. Hallmarks of exercised heart. J Mol Cell Cardiol 2022; 164: 126-35.
[http://dx.doi.org/10.1016/j.yjmcc.2021.12.004] [PMID: 34914934]
[http://dx.doi.org/10.1016/j.yjmcc.2021.12.004] [PMID: 34914934]
[26]
Keller TCS IV, Lim L, Shewale SV, et al. Genetic blockade of lymphangiogenesis does not impair cardiac function after myocardial infarction. J Clin Invest 2021; 131(20): e147070.
[http://dx.doi.org/10.1172/JCI147070] [PMID: 34403369]
[http://dx.doi.org/10.1172/JCI147070] [PMID: 34403369]
Article Metrics
7