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Exosomes Released From Human Induced Pluripotent Stem Cells-Derived MSCs Facilitate Cutaneous Wound Healing by Promoting Collagen Synthesis and Angiogenesis

Exosomes Released From Human Induced Pluripotent Stem Cells-Derived MSCs Facilitate Cutaneous Wound Healing by Promoting Collagen Synthesis and Angiogenesis

Jieyuan Zhang, Junjie Guan, Xin Niu, Guowen Hu, Shangchun Guo, Qing Li, Zongping Xie, Changqing Zhang, Yang Wang

J Transl Med. 2015 Feb 1;13:49.

PMID: 25638205

Abstract:

Background:
Human 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.
Methods:
hiPSC-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.
Results:
Transplanting 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.
Conclusions:
Our 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP9007583-G	α-Elastin from rat		9007-58-3	Price

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