Xiangnan Zhao1,2, Yue Liu1, Pingping Jia3, Hui Cheng1, Chen Wang1, Shang Chen1, Haoyan Huang1, Zhibo Han4,5,6, Zhong-Chao Han4,5,6, Krzysztof Marycz7, Xiaoniao Chen8, Zongjin Li9,10,11. 1. Nankai University School of Medicine, 94 Weijin Road, Tianjin, 300071, China. 2. The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, 300071, China. 3. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, 453003, China. 4. Jiangxi Engineering Research Center for Stem Cell, Shangrao, 334109, Jiangxi, China. 5. Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin, 300457, China. 6. Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing, 100176, China. 7. Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland. 8. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. birdchen512@qq.com. 9. Nankai University School of Medicine, 94 Weijin Road, Tianjin, 300071, China. zongjinli@nankai.edu.cn. 10. The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, The College of Life Sciences, Tianjin, 300071, China. zongjinli@nankai.edu.cn. 11. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, 453003, China. zongjinli@nankai.edu.cn.
Abstract
BACKGROUND: The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment. METHODS: In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking. RESULTS: CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures. CONCLUSIONS: CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.
BACKGROUND: The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment. METHODS: In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking. RESULTS:CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures. CONCLUSIONS:CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.
Authors: Xinpeng Yao; Yi Liu; Jie Gao; Liang Yang; Duo Mao; Christina Stefanitsch; Yang Li; Jun Zhang; Lailiang Ou; Deling Kong; Qiang Zhao; Zongjin Li Journal: Biomaterials Date: 2015-05-16 Impact factor: 12.479
Authors: Jean-Philippe Coppé; Christopher K Patil; Francis Rodier; Ana Krtolica; Christian M Beauséjour; Simona Parrinello; J Graeme Hodgson; Koei Chin; Pierre-Yves Desprez; Judith Campisi Journal: PLoS One Date: 2010-02-12 Impact factor: 3.240