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Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis.
J Transl Med 2015; 13:49JT

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.

Authors+Show Affiliations

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. wuzongxiange@126.com. Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. wuzongxiange@126.com.Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. junjie_guan@126.com. Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. junjie_guan@126.com.Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. niuxin999@163.com.Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. hugw0625@163.com. Graduate School of Nanchang University, Nanchang, Jiangxi, China. hugw0625@163.com.Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 1321165979@qq.com.Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. liqing236@gmail.com.Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. x91034@qq.com.Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. zhangcq@sjtu.edu.cn. Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. zhangcq@sjtu.edu.cn.Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. wangy63cn@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25638205

Citation

Zhang, Jieyuan, et al. "Exosomes Released From Human Induced Pluripotent Stem Cells-derived MSCs Facilitate Cutaneous Wound Healing By Promoting Collagen Synthesis and Angiogenesis." Journal of Translational Medicine, vol. 13, 2015, p. 49.
Zhang J, Guan J, Niu X, et al. Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. J Transl Med. 2015;13:49.
Zhang, J., Guan, J., Niu, X., Hu, G., Guo, S., Li, Q., ... Wang, Y. (2015). Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. Journal of Translational Medicine, 13, p. 49. doi:10.1186/s12967-015-0417-0.
Zhang J, et al. Exosomes Released From Human Induced Pluripotent Stem Cells-derived MSCs Facilitate Cutaneous Wound Healing By Promoting Collagen Synthesis and Angiogenesis. J Transl Med. 2015 Feb 1;13:49. PubMed PMID: 25638205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exosomes released from human induced pluripotent stem cells-derived MSCs facilitate cutaneous wound healing by promoting collagen synthesis and angiogenesis. AU - Zhang,Jieyuan, AU - Guan,Junjie, AU - Niu,Xin, AU - Hu,Guowen, AU - Guo,Shangchun, AU - Li,Qing, AU - Xie,Zongping, AU - Zhang,Changqing, AU - Wang,Yang, Y1 - 2015/02/01/ PY - 2014/11/01/received PY - 2015/01/22/accepted PY - 2015/2/2/entrez PY - 2015/2/2/pubmed PY - 2016/3/15/medline SP - 49 EP - 49 JF - Journal of translational medicine JO - J Transl Med VL - 13 N2 - 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. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/25638205/Exosomes_released_from_human_induced_pluripotent_stem_cells_derived_MSCs_facilitate_cutaneous_wound_healing_by_promoting_collagen_synthesis_and_angiogenesis_ L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-015-0417-0 DB - PRIME DP - Unbound Medicine ER -