Abstract
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton’s jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo. A significant increase in HaCaT proliferation was observed with iMSC-exo, although both exosomes increased the viability and cell cycle progression in HaCaT and HDFs. No significant difference was observed in the closure of wound scratch and the expression of reparative genes between cells treated with the two exosome types. Both exosomes enhanced the secretion of collagen in HaCaT and HDFs; however, an increase in fibronectin level was observed only in HaCaT, and this effect was better with iMSC-exo treatment. Only iMSC-exo increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. Our results indicate that iMSC-exo promote the proliferation of skin cells by stimulating ERK1/2 and highlight the application of iMSCs for producing exosomes.
Highlights
Skin wound healing is characterized by continuous tissue regeneration orchestrated by multiple cells in the epidermal and dermal layers to re-establish the barrier [1]
Our findings demonstrate that exosome from iMSCs exert superior functions as compared with exosomes derived from naïve mesenchymal stem cells (MSCs) (MSC-exo), which is suggestive of their potential application for cell-free skin regeneration strategies
We sought to investigate whether exosomes secreted from iMSCs can stimulate the proliferation of keratinocytes and dermal fibroblasts, the essential players in skin regeneration
Summary
Skin wound healing is characterized by continuous tissue regeneration orchestrated by multiple cells in the epidermal and dermal layers to re-establish the barrier [1]. Fibroblasts move to the wound site in a spatio-temporal manner and release soluble factors such as growth factors and cytokines and produce the extracellular matrix (ECM) to reconstitute the dermal layer [2] Despite this well-coordinated response against damage signals, the natural processes of re-epithelialization and dermal repair may be insufficient in severe pathological conditions such as burns, trauma, and diabetes, which necessitate the development of alternative therapeutic strategies such as the use of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs) [3]. Mesenchymal stem cells are progenitor cells of connective tissues (osteoblasts, chondrocytes, and adipocytes) with significant immunoregulatory and regenerative functions [4] Despite their potential therapeutic applications, current technology faces several hurdles such as low viability of the transplanted cells, innate heterogenicity, unidentified factors related to aging of the donor, and potential tumorigenicity [5]. Among EV subpopulation, exosome is gaining increasing interests in immune modulation and regenerative therapy [6,8,9]
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