Promoting skin cell regeneration -
Thus, they involve cell signalling and cell-to-cell communication and they influence tissue responses to injury, infection and disease [ 14 , 28 ].
In this study, we found that the primary function of promoting skin healing and reducing scar formation may be caused by EPSC-Exos-specific miRNAs.
The EPSC-Exos-specific miRNAs inhibited myofibroblast formation, which might be related to the targeting of TGF-β1-targeting microRNAs. In our previous study, several highly expressed specific microRNAs derived from EPSC-Exos were identified, including miR, let-7a, miRp and miRp.
miRp [ 29 ] and miRp [ 30 ] have been previously reported to suppress fibrotic diseases, and most studies have suggested that these two microRNAs directly target TGF-β1, consistent with our present findings. We believe the functions of microRNAs in different organs and tissues might be the same.
We believe these EPSC-Exos miRNAs could be essential inhibitors of TGF-β1, reducing the myofibroblast formation during skin wound healing. Exosome-derived microRNAs are more stable than their parental cells. They can resist degradation in the circulation process in the body through the vesicle structure released by the parental cells [ 18 , 31 ].
In the subsequent production and application, we can use EPSC as a factory to produce exosomes, making EPSC produce more functional microRNAs via transfection. Compared with EPSC, EPSC-Exos might be safer and more efficient in clinical applications.
They may also have other advantages, such as easier storage and production, a lower risk of side effects and easier quality control. Thus, we suggest that EPSC-Exos could be a candidate strategy for promoting healing and reducing scar formation in the future. This study has shed light on the specific microRNAs of EPSC-Exos and clarified a new approach for using stem cell therapy to promote wound healing and reduce scarring.
miRp and miRp from EPSC-Exos might suppress myofiber and collagen I deposition via downregulating TGF-β1 expression Fig.
As an alternative to cell therapy, EPSC-Exos might have a clinically beneficial anti-scarring effect. EPSC-Exos promoted wound healing and reduced scarring. MiRp and miRp carried by EPSC-Exos might suppress myofiber and collagen I deposition via downregulating TGF-β1 expression.
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J Transl Med. Download references. We thank Professor Wang from the China-Japan Union Hospital of Jilin University for providing the epidermal stem cells and human dermal fibroblasts. This work was supported by the Jilin Provincial Department of Education Science and Technology Program China, No.
JJKHKJ and Science and Technology Project of Jilin Provincial Finance Department China, No. Department of Prosthodontics, Hospital of Stomatology, Jilin University, Qinghua Rd. Jilin Provincial Laboratory of Biomedical Engineering, Jilin University, Qinghua Rd. Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Pudong Rd.
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MD and GZ designed and supervised the research; YZ performed the research and analysed the data; HZ and MQ contributed to animal experiments; MD and YM contributed to histopathological experiments; and MD, MQ and GZ wrote and edited the paper.
All authors read and approved the final manuscript. Correspondence to Ming Qian or Guokun Zhang. This study was approved by the Administration Committee of Experimental Animals Jilin University Approval No.
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Duan, M. et al. Epidermal stem cell-derived exosomes promote skin regeneration by downregulating transforming growth factor-β1 in wound healing. Stem Cell Res Ther 11 , Download citation.
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Search all BMC articles Search. Download PDF. Abstract Background Scar formation, which may be caused by myofibroblast aggregations, is the greatest challenge during skin wound healing in the clinical setting.
Methods We investigated the therapeutic effects of EPSC-derived exosomes EPSC-Exos on skin wound healing in a skin-defect rat model. Results We found that EPSC-Exos increased the wound healing rate and reduced scar formation in rats.
Conclusion We found a novel function of EPSC-Exos-specific microRNAs, suggesting that EPSC-Exos might represent a strategy to prevent scar formation during wound healing in the clinical setting. Background The skin is a multilayer interface between the body and the environment, which can regulate temperature, prevent dehydration, keep out pathogens, provide sensation and transport water [ 1 , 2 , 3 ].
Materials and methods Cell culture The cell lines of EPSC and human dermal fibroblasts HDF were obtained from the China-Japan Union Hospital of Jilin University. Exosome isolation EPSC-Exos were purified by ultracentrifugation according to previously reported methods [ 15 , 18 ].
Histopathological analysis Skin tissue was embedded in paraffin, then sliced into 4-μm sections. qRT-PCR Trizol reagent Tiangen, Beijing, China was used for total RNA isolation of the skin tissue. Results EPSC-Exos improve wound healing rate and suppress scar formation We first identified the purified EPSC-Exos.
Full size image. Discussion Scar formation is an undesirable and significant result of both wound healing and fibrosing disorders. Conclusions This study has shed light on the specific microRNAs of EPSC-Exos and clarified a new approach for using stem cell therapy to promote wound healing and reduce scarring.
Abbreviations α-SMA: α-Smooth muscle actin CD Platelet endothelial cell adhesion molecule-1 EGF: Epidermal growth factor EPSC: Epidermal stem cells EPSC-Exos: EPSC-derived exosomes HDF: Human dermal fibroblasts IF: Immunofluorescence staining IHC: Immunohistochemical staining PBS: Phosphate-buffered saline TGF-β1: Transforming growth factor-β1.
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Elodie Labit, PhD, postdoctoral fellow. Progenitor cells are unique in that they are able to undergo cell division and generate many new cells to either maintain or repair tissues. Using cutting-edge genomics techniques to profile thousands of individual cells at different times after injury, the research team compared scar-forming versus regenerative zones within skin wounds.
Whereas in scar-forming zones, these pro-regenerative programs are absent or suppressed and scar-forming programs dominate. This research offers critical insights into the molecular signals that drive scar formation during wound healing and it identifies a number of genetic signals that are able to overcome fibrosis and promote true regeneration of adult skin.
Our hope is to develop a cocktail of drugs that we could safely administer in humans and animals to entirely prevent genetic programs that initiate scar formation in order to greatly improve the quality of skin healing.
Additional authors on the study from UCVM include Dr. Nicole Rosin, PhD, Grace Yoon, Dr. Andrew Hagner, PhD, Prajay Shah, Rohit Arora, Jessica Yoon and Dr.
Jo Anne Stratton, PhD. The study was funded by the Canadian Institutes of Health Research and the Calgary Firefighters Burn Treatment Society.
Jeff Biernaskie is a professor in the Department of Comparative Biology and Experimental Medicine in the Faculty of Veterinary Medicine and the Calgary Firefighters Burn Treatment Society Chair.
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