Chitosan hydrogel-loaded MSC-derived extracellular vesicles promote skin rejuvenation by ameliorating the senescence of dermal fibroblasts
Xiangnan Zhao , Yue Liu , Pingping Jia , Hui Cheng , Chen Wang , Shang Chen , Haoyan Huang , Zhibo Han , Zhong-Chao Han , Krzysztof Marycz , Xiaoniao Chen , Zongjin Li
AbstractBackground: 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.
|Journal series||Stem Cell Research & Therapy, [Stem Cell Research and Therapy], ISSN 1757-6512, (N/A 100 pkt)|
|Publication size in sheets||0.7|
|Keywords in English||Extracellular vesicles (EVs); Chitosan hydrogel; Dermal fibroblasts (DFLs); Skin aging; Extracellular matrix (ECM)|
|ASJC Classification||; ; ;|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 10-05-2021, ArticleFromJournal|
|Publication indicators||= 0; = 0; : 2017 = 1.266; : 2018 = 4.627 (2) - 2018=5.363 (5)|
|Citation count*||1 (2021-05-09)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.