Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Cutaneous wound healing represents a morphogenetic response to injury and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cell-derived exosomes (hBM-MSC-Ex) are a promising source for cell-free therapy and skin regeneration.

Methods

In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSC-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSC-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSC-Ex on cutaneous wound healing in vivo.

Results

The results demonstrated that hBM-MSC-Ex promote both two types of skin cells’ growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSC-Ex significantly downregulated TGF-β1, Smad2, Smad3, and Smad4 expression, while upregulated TGF-β3 and Smad7 expression in the TGF-β/Smad signaling pathway.

Conclusions

Our findings indicated that hBM-MSC-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-β/Smad signal pathway. The current results provided a new sight for the therapeutic strategy for the treatment of cutaneous wounds.

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

New insights into TGF-β/Smad signaling in tissue fibrosis

Ying-Yong Zhao, He-He Hu, Dan-Qian Chen … (2018)

Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.

0 comments Cited 340 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Fibroblasts and myofibroblasts in wound healing

Ian Darby, Betty Laverdet, Frédéric Bonté … (2014)

(Myo)fibroblasts are key players for maintaining skin homeostasis and for orchestrating physiological tissue repair. (Myo)fibroblasts are embedded in a sophisticated extracellular matrix (ECM) that they secrete, and a complex and interactive dialogue exists between (myo)fibroblasts and their microenvironment. In addition to the secretion of the ECM, (myo)fibroblasts, by secreting matrix metalloproteinases and tissue inhibitors of metalloproteinases, are able to remodel this ECM. (Myo)fibroblasts and their microenvironment form an evolving network during tissue repair, with reciprocal actions leading to cell differentiation, proliferation, quiescence, or apoptosis, and actions on growth factor bioavailability by binding, sequestration, and activation. In addition, the (myo)fibroblast phenotype is regulated by mechanical stresses to which they are subjected and thus by mechanical signaling. In pathological situations (excessive scarring or fibrosis), or during aging, this dialogue between the (myo)fibroblasts and their microenvironment may be altered or disrupted, leading to repair defects or to injuries with damaged and/or cosmetic skin alterations such as wrinkle development. The intimate dialogue between the (myo)fibroblasts and their microenvironment therefore represents a fascinating domain that must be better understood in order not only to characterize new therapeutic targets and drugs able to prevent or treat pathological developments but also to interfere with skin alterations observed during normal aging or premature aging induced by a deleterious environment.

0 comments Cited 296 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis

Kelly Walton, Katharine Johnson, Craig Harrison (2017)

Fibrosis occurs when there is an imbalance in extracellular matrix (ECM) deposition and degradation. Excessive ECM deposition results in scarring and thickening of the affected tissue, and interferes with tissue and organ homeostasis – mimicking an exaggerated “wound healing” response. Many transforming growth factor-β (TGF-β) ligands are potent drivers of ECM deposition, and additionally, have a natural affinity for the ECM, creating a concentrated pool of pro-fibrotic factors at the site of injury. Consequently, TGF-β ligands are upregulated in many human fibrotic conditions and, as such, are attractive targets for fibrosis therapy. Here, we will discuss the contribution of TGF-β proteins in the pathogenesis of fibrosis, and promising anti-fibrotic approaches that target TGF-β ligands.

0 comments Cited 169 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Tiechao Jiang: jiangtc@jlu.edu.cn

Journal

Journal ID (nlm-ta): Stem Cell Res Ther

Journal ID (iso-abbrev): Stem Cell Res Ther

Title: Stem Cell Research & Therapy

Publisher: BioMed Central (London )

ISSN (Electronic): 1757-6512

Publication date (Electronic): 24 May 2020

Publication date PMC-release: 24 May 2020

Publication date Collection: 2020

Volume: 11

Electronic Location Identifier: 198

Affiliations

[1 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, Department of Cardiology, , The Third Hospital of Jilin University, ; 126 Xiantai St., Changchun, 130033 Jilin China

[2 ]Jilin Provincial Cardiovascular Research Institute, 126 Xiantai St., Changchun, 130033 Jilin China

[3 ]GRID grid.430605.4, Department of Pediatric Neurology, , The First Hospital of Jilin University, ; 71 Xinmin St., Changchun, 130021 Jilin China

Article

Publisher ID: 1723

DOI: 10.1186/s13287-020-01723-6

PMC ID: 7245763

PubMed ID: 32448395

SO-VID: 2b653692-8100-46e5-89ec-104ca1ababb9

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 February 2020

Date revision received : 6 May 2020

Date accepted : 11 May 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81570360

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: human bone marrow mesenchymal stem cells,exosomes,wound healing,tgf-β/smad signaling

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: human bone marrow mesenchymal stem cells, exosomes, wound healing, tgf-β/smad signaling

Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-β/Smad signaling pathway

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Neuronal Signaling

Most cited references 33

New insights into TGF-β/Smad signaling in tissue fibrosis

Fibroblasts and myofibroblasts in wound healing

Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 373

Cited by 53

Most referenced authors 859