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Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization.
Int J Mol Sci. 2019 Jan 09; 20(2)IJ

Abstract

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch's membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy.

Authors+Show Affiliations

Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. backyard0826@gmail.com.Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. g39005005@gmail.com. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. g39005005@gmail.com.Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. s19609005@gm.ym.edu.tw.Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. monglien@gmail.com. Facility of Medicine, School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. monglien@gmail.com.Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. yarmishyn@gmail.com.Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan. molly0103@gmail.com.Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan. m95gbk@hotmail.com. Department of Public Health and Institute of Public Health, National Yang-Ming University, Taipei 11217, Taiwan. m95gbk@hotmail.com.Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital & Fu-Jen Catholic University, Taipei 11101, Taiwan. chpeng1008@gmail.com. Institute of Clinical Medicine, National Yang-Ming University, Taipei 11217, Taiwan. chpeng1008@gmail.com.Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan. chihchienym@gmail.com. Institute of Clinical Medicine, National Yang-Ming University, Taipei 11217, Taiwan. chihchienym@gmail.com.Facility of Medicine, School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. sjchen96@gmail.com. Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan. sjchen96@gmail.com.Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11217, Taiwan. yred8530@gmail.com. Department of Ophthalmology, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan. yred8530@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30634448

Citation

Lin, Tzu-Wei, et al. "Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization." International Journal of Molecular Sciences, vol. 20, no. 2, 2019.
Lin TW, Chien Y, Lin YY, et al. Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization. Int J Mol Sci. 2019;20(2).
Lin, T. W., Chien, Y., Lin, Y. Y., Wang, M. L., Yarmishyn, A. A., Yang, Y. P., Hwang, D. K., Peng, C. H., Hsu, C. C., Chen, S. J., & Chien, K. H. (2019). Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization. International Journal of Molecular Sciences, 20(2). https://doi.org/10.3390/ijms20020241
Lin TW, et al. Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization. Int J Mol Sci. 2019 Jan 9;20(2) PubMed PMID: 30634448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization. AU - Lin,Tzu-Wei, AU - Chien,Yueh, AU - Lin,Yi-Ying, AU - Wang,Mong-Lien, AU - Yarmishyn,Aliaksandr A, AU - Yang,Yi-Ping, AU - Hwang,De-Kuang, AU - Peng,Chi-Hsien, AU - Hsu,Chih-Chien, AU - Chen,Shih-Jen, AU - Chien,Ke-Hung, Y1 - 2019/01/09/ PY - 2018/10/23/received PY - 2018/12/15/revised PY - 2018/12/26/accepted PY - 2019/1/13/entrez PY - 2019/1/13/pubmed PY - 2019/4/24/medline KW - age-related macular degeneration (AMD) KW - induced pluripotent stem cells (iPSCs) KW - polydimethylsiloxane (PDMS) KW - retinal pigment epithelial (RPE) cells KW - vascular endothelial growth factor (VEGF) JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 2 N2 - Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch's membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30634448/Establishing_Liposome_Immobilized_Dexamethasone_Releasing_PDMS_Membrane_for_the_Cultivation_of_Retinal_Pigment_Epithelial_Cells_and_Suppression_of_Neovascularization_ L2 - https://www.mdpi.com/resolver?pii=ijms20020241 DB - PRIME DP - Unbound Medicine ER -