Abstract
BackgroundThe 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.MethodsIn 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.ResultsCS-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.ConclusionsCS 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.
Highlights
Aging is an unavoidable process for everyone
The characterization of extracellular vesicles (EVs) was demonstrated by transmission electron microscopy (TEM), dynamic light scattering (DLS), and Western blot analysis
The size of EVs was determined by DLS, and the results showed that the average particle diameter is about 120 nm (Fig. 1b)
Summary
Aging is an unavoidable process for everyone. The most evident and visible symptoms of aging in humans are first manifested by changing skin appearances, such as skin sagging, loss of elasticity, and wrinkle formation [1]. It is generally believed that skin aging is driven by various intrinsic and extrinsic factors, including various kinds of skin cell senescence [2]. Thereinto, dermal fibroblasts (DFLs) are the main skin stromal cells that secrete extracellular matrix (ECM). DFLs can synthesize and secrete ECM components such as collagen, elastin, and hyaluronic acid, which are processed to assemble fibers, giving the skin elasticity and toughness and helping to keep the juvenescence of skin [3]. During the aging processes, ECM is gradually degraded and disorganized, which will deleteriously alter the function of resident fibroblasts. 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 leads to skin aging. 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
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