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http://dx.doi.org/10.5713/ajas.20.0202

Conjugation of vascular endothelial growth factor to poly lactic-co-glycolic acid nanospheres enhances differentiation of embryonic stem cells to lymphatic endothelial cells  

Yoo, Hyunjin (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced and Regenerative Science, Konkuk University)
Choi, Dongyoon (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced and Regenerative Science, Konkuk University)
Choi, Youngsok (Department of Stem Cell and Regenerative Biotechnology, Institute of Advanced and Regenerative Science, Konkuk University)
Publication Information
Animal Bioscience / v.34, no.4, 2021 , pp. 533-538 More about this Journal
Abstract
Objective: Pluripotent stem cell-derived lymphatic endothelial cells (LECs) show great promise in their therapeutic application in the field of regenerative medicine related to lymphatic vessels. We tested the approach of forced differentiation of mouse embryonal stem cells into LECs using biodegradable poly lactic-co-glycolic acid (PLGA) nanospheres in conjugation with growth factors (vascular endothelial growth factors [VEGF-A and VEGF-C]). Methods: We evaluated the practical use of heparin-conjugated PLGA nanoparticles (molecular weight ~15,000) in conjugation with VEGF-A/C, embryoid body (EB) formation, and LEC differentiation using immunofluorescence staining followed by quantification and quantitative real-time polymerase chain reaction analysis. Results: We showed that formation and differentiation of EB with VEGF-A/C-conjugated PLGA nanospheres, compared to direct supplementation of VEGF-A/C to the EB differentiation media, greatly improved yield of LYVE1(+) LECs. Our analyses revealed that the enhanced potential of LEC differentiation using VEGF-A/C-conjugated PLGA nanospheres was mediated by elevation of expression of the genes that are important for lymphatic vessel formation. Conclusion: Together, we not only established an improved protocol for LEC differentiation using PLGA nanospheres but also provided a platform technology for the mechanistic study of LEC development in mammals.
Keywords
Stem Cell; Lymphatic Endothelial Cell; Poly Lactic-co-glycolic Acid (PLGA);
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1 Norrmen C, Ivanov KI, Cheng J, et al. FOXC2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1. J Cell Biol 2009;185:439-57. https://doi.org/10.1083/jcb.200901104   DOI
2 Irrthum A, Devriendt K, Chitayat D, et al. Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. Am J Hum Genet 2003;72:1470-8. https://doi.org/10.1086/375614   DOI
3 Mehrara BJ, Greene AK. Lymphedema and obesity: is there a link? Plast Reconstr Surg 2014;134:154e-60e. https://doi.org/10.1097/PRS.0000000000000268   DOI
4 Cueni LN, Detmar M. The lymphatic system in health and disease. Lymphat Res Biol 2008;6:109-22. http://doi.org/10.1089/lrb.2008.1008   DOI
5 Baluk P, Fuxe J, Hashizume H, et al. Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 2007;204:2349-62. https://doi.org/10.1084/jem.20062596   DOI
6 Yu P, Tung JK, Simons M. Lymphatic fate specification: an ERK-controlled transcriptional program. Microvasc Res 2014;96:10-5. https://doi.org/10.1016/j.mvr.2014.07.016   DOI
7 Pichol-Thievend C, Hogan BM, Francois M. Lymphatic vascular specification and its modulation during embryonic development. Microvasc Res 2014;96:3-9. https://doi.org/10.1016/j.mvr.2014.07.011   DOI
8 Tammela T, Alitalo K. Lymphangiogenesis: molecular mechanisms and future promise. Cell 2010;140:460-76. https://doi.org/10.1016/j.cell.2010.01.045   DOI
9 Makinen T, Veikkola T, Mustjoki S, et al. Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J 2001;20:4762-73. https://doi.org/10.1093/emboj/20.17.4762   DOI
10 Karkkainen MJ, Haiko P, Sainio K, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol 2004;5:74-80. https://doi.org/10.1038/ni1013   DOI
11 Schulte-Merker S, Sabine A, Petrova TV. Lymphatic vascular morphogenesis in development, physiology, and disease. J Cell Biol 2011;193:607-18. https://doi.org/10.1083/jcb.201012094   DOI
12 Kunstfeld R, Hirakawa S, Hong YK, et al. Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia. Blood 2004;104:1048-57. https://doi.org/10.1182/blood-2003-08-2964   DOI
13 Lee SJ, Park C, Lee JY, et al. Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair. Sci Rep 2015;5:11019. https://doi.org/10.1038/srep11019   DOI
14 Kreuger J, Nilsson I, Kerjaschki D, Petrova T, Alitalo K, Claesson-Welsh L. Early lymph vessel development from embryonic stem cells. Arterioscler Thromb Vasc Biol 2006;26:1073-8. https://doi.org/10.1161/01.ATV.0000217610.58032.b7   DOI
15 Kono T, Kubo H, Shimazu C, et al. Differentiation of lymphatic endothelial cells from embryonic stem cells on OP9 stromal cells. Arterioscler Thromb Vasc Biol 2006;26:2070-6. https://doi.org/10.1161/01.ATV.0000225770.57219.b0   DOI
16 Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature 2005;438:946-53. https://doi.org/10.1038/nature04480   DOI
17 Lee MS, Ahmad T, Lee J, et al. Dual delivery of growth factors with coacervate-coated poly(lactic-co-glycolic acid) nanofiber improves neovascularization in a mouse skin flap model. Biomaterials 2017;124:65-77. https://doi.org/10.1016/j.biomaterials.2017.01.036   DOI
18 La WG, Yang HS. Heparin-conjugated poly(lactic-co-glycolic acid) nanospheres enhance large-wound healing by delivering growth factors in platelet-rich plasma. Artif Organs 2015;39:388-94. https://doi.org/10.1111/aor.12389   DOI
19 La WG, Kang SW, Yang HS, et al. The efficacy of bone morphogenetic protein-2 depends on its mode of delivery. Artif Organs 2010;34:1150-3. https://doi.org/10.1111/j.1525-1594.2009.00988.x   DOI
20 Jeon O, Kang SW, Lim HW, Chung JH, Kim BS. Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel. Biomaterials 2006;27:1598-607. https://doi.org/10.1016/j.biomaterials.2005.08.030   DOI
21 Yang K, Park E, Lee JS, et al. Biodegradable nanotopography combined with neurotrophic signals enhances contact guidance and neuronal differentiation of human neural stem cells. Macromol Biosci 2015;15:1348-56. https://doi.org/10.1002/mabi.201500080   DOI
22 Francois M, Caprini A, Hosking B, et al. Sox18 induces development of the lymphatic vasculature in mice. Nature 2008;456:643-7. https://doi.org/10.1038/nature07391   DOI
23 Niessen K, Zhang G, Ridgway JB, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood 2010;115:1654-61. https://doi.org/10.1182/blood2009-07-235655   DOI
24 Moon EH, Kim YS, Seo J, Lee S, Lee YJ, Oh SP. Essential role for TMEM100 in vascular integrity but limited contributions to the pathogenesis of hereditary haemorrhagic telangiectasia. Cardiovasc Res 2015;105:353-60. https://doi.org/10.1093/cvr/cvu260   DOI
25 Koltowska K, Betterman KL, Harvey NL, Hogan BM. Getting out and about: the emergence and morphogenesis of the vertebrate lymphatic vasculature. Development 2013;140:1857-70. https://doi.org/10.1242/dev.089565   DOI
26 Liersch R, Nay F, Lu L, Detmar M. Induction of lymphatic endothelial cell differentiation in embryoid bodies. Blood 2006;107:1214-6. https://doi.org/10.1182/blood-2005-08-3400   DOI
27 Pan Y, Wang W, Yago T. Transcriptional regulation of podoplanin expression by Prox1 in lymphatic endothelial cells. Microvasc Res 2014;94:96-102. https://doi.org/10.1016/j.mvr.2014.05.006   DOI