Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis

Abstract

BackgroundHuman induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC-MSCs) have emerged as a promising alternative for stem cell transplantation therapy. Exosomes derived from mesenchymal stem cells (MSC-Exos) can play important roles in repairing injured tissues. However, to date, no reports have demonstrated the use of hiPSC-MSC-Exos in cutaneous wound healing, and little is known regarding their underlying mechanisms in tissue repair.MethodshiPSC-MSC-Exos were injected subcutaneously around wound sites in a rat model and the efficacy of hiPSC-MSC-Exos was assessed by measuring wound closure areas, by histological and immunofluorescence examinations. We also evaluated the in vitro effects of hiPSC-MSC-Exos on both the proliferation and migration of human dermal fibroblasts and human umbilical vein endothelial cells (HUVECs) by cell-counting and scratch assays, respectively. The effects of exosomes on fibroblast collagen and elastin secretion were studied in enzyme-linked immunosorbent assays and quantitative reverse-transcriptase–polymerase chain reaction (qRT-PCR). In vitro capillary network formation was determined in tube-formation assays.ResultsTransplanting hiPSC-MSC-Exos to wound sites resulted in accelerated re-epithelialization, reduced scar widths, and the promotion of collagen maturity. Moreover, hiPSC-MSC-Exos not only promoted the generation of newly formed vessels, but also accelerated their maturation in wound sites. We found that hiPSC-MSC-Exos stimulated the proliferation and migration of human dermal fibroblasts and HUVECs in a dose-dependent manner in vitro. Similarly, Type I, III collagen and elastin secretion and mRNA expression by fibroblasts and tube formation by HUVECs were also increased with increasing hiPSC-MSC-Exos concentrations.ConclusionsOur findings suggest that hiPSC-MSC-Exos can facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. These data provide the first evidence for the potential of hiPSC-MSC-Exos in treating cutaneous wounds.

Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing

“…MSCbased therapies have been shown to induce a complex process of interactions among numerous types of cells, components of the extracellular matrix, and signaling molecules after injury. Such therapies have been reported to promote wound healing, maintain cutaneous homeostasis, and reduce scar formation [27,28]. Most previous studies were aimed at deciphering the mechanism of the healing promoting effects of MSC-based therapies.…”

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

“…Exosomes were extracted and purified according to previous protocols [39,40]. Briefly, uMSCs were cultured in DMEM with 10% FBS, which was pretreated by ultracentrifugation at 120,000 g overnight at 4°C to remove serum exosomes in T75 or T150 flasks.…”

Exosomes as a novel pathway for regulating development and diseases of the skin (Review)

“…However, cells derived from different sources, including adipose mesenchymal cells and human amniotic epithelial cells, have demonstrated similar characteristics to MSCs (63). Exosomes of endothelial progenitor cells from human umbilical cord blood may also accelerate skin wound healing (64).…”

“…Exosomes of endothelial progenitor cells from human umbilical cord blood may also accelerate skin wound healing (64). Exosomes released from human induced pluripotent stem cell-derived MSCs have the ability of tissue repair by promoting collagen synthesis and angiogenesis (63). Similarly, exosomes secreted by cardiosphere-derived cells contribute to scar reduction (65).…”