Exosomes Derived from Human Induced Pluripotent Stem Cells Ameliorate the Aging of Skin Fibroblasts

Abstract

Stem cells and their paracrine factors have emerged as a resource for regenerative medicine. Many studies have shown the beneficial effects of paracrine factors secreted from adult stem cells, such as exosomes, on skin aging. However, to date, few reports have demonstrated the use of exosomes derived from human pluripotent stem cells for the treatment of skin aging. In this study, we collected exosomes from the conditioned medium of human induced pluripotent stem cells (iPSCs) and investigated the effect on aged human dermal fibroblasts (HDFs). Cell proliferation and viability were determined by an MTT assay and cell migration capacity was shown by a scratch wound assay and a transwell migration assay. To induce photoaging and natural senescence, HDFs were irradiated by UVB (315 nm) and subcultured for over 30 passages, respectively. The expression level of certain mRNAs was evaluated by quantitative real-time PCR (qPCR). Senescence-associated-β-galactosidase (SA-β-Gal) activity was assessed as a marker of natural senescence. As a result, we found that exosomes derived from human iPSCs (iPSCs-Exo) stimulated the proliferation and migration of HDFs under normal conditions. Pretreatment with iPSCs-Exo inhibited the damages of HDFs and overexpression of matrix-degrading enzymes (MMP-1/3) caused by UVB irradiation. The iPSCs-Exo also increased the expression level of collagen type I in the photo-aged HDFs. In addition, we demonstrated that iPSCs-Exo significantly reduced the expression level of SA-β-Gal and MMP-1/3 and restored the collagen type I expression in senescent HDFs. Taken together, it is anticipated that these results suggest a therapeutic potential of iPSCs-Exo for the treatment of skin aging.

Highly Purified Human Extracellular Vesicles Produced by Stem Cells Alleviate Aging Cellular Phenotypes of Senescent Human Cells

“…These studies have provoked great interest in examining the roles of EVs in cellular senescence and aging [45]. During the preparation of this article, Park et al published a paper showing that human iPSC-EVs ameliorated aging of skin fibroblasts in vitro using an irradiation model [46]. Together, these studies firmly demonstrate that iPSC-EVs and MSC-EVs can alleviate senescence of human cells in vitro.…”

Human Pluripotent Stem Cell-Derived Extracellular Vesicles: Characteristics and Applications

“…68,69 hiPSC-exosomes were also reported to stimulate the proliferation and migration of human dermal fibroblasts. 70 In addition, hiPSC-EVs or exosomes reduced MMP-1/-3 expression and restored the collagen I expression in senescent skin fibroblast cells, showing the potential in treating skin aging. iPSC-EVs (about 300 nm) also reduced hepatic stellate cell activation and liver fibrosis, showing the ability to decrease profibrogenic markers a-smooth muscle actin, collagen Ia1, and fibronectin, and tissue inhibitor of metalloproteinases-1.…”

miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence

“…For example, ECM-receptor interaction is an important pathway among them. 12 In addition, it has been proven that adenosine monophosphate-activated protein kinase plays a pivotal function in the aging process and longevity of lower organisms. The skin aging process is governed by dermis ECM.…”