The function of exosomes in wound healing

Samin Abdolzadeh,1,* Maryam taghavi narmi,2 Asiyeh jebelli,3

1. Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid , Tabriz , Iran
2. Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid , Tabriz , Iran
3. Department of Biological Science, Faculty of Basic Science, Higher Education Institute of Rab-Rashid , Tabriz , Iran

Abstract

Introduction

Exosomes are biological nanoparticle molecules which have a role in a paracrine and endocrine signaling as the intracellular markers. they have been found in physiological fluids such as urine, plasma, cerebrospinal fluid, and human milk and can be transferred between cells to mediating cell-to-cell communication and interactions. they are involved in many processes including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. exosomes contain proteins (membrane proteins, endosome-associated proteins, and lipid raft protein), rnas (structural rnas, trna fragments, vault rna, y rna and mirnas), signaling lipids, cytokines and growth factors. exosomes release components that due to lack of a signal sequence can not be secreted by the usual transport pathway between er and golgi.

Methods

Recent studies have demonstrated that exosomes can influence tissue responses to different status such injuries, infections, tumorigenesis and disease. they are one of the key secretory products of various cell type especially adipose mesenchymal stem cells (amscs) to regulate tissue regeneration like wound healing and restore tissue and organ damage. hence, understanding these exosomes effects may help to improve wound management and highlight a new therapeutic model for cell-free therapies with decreased side effects for the wound repair.

Results

Initial studies reported that the therapeutic potency of amscs was due to the fact that they easily differentiate into various cell types such as chondrocytes, adipocytes, osteoblasts or endothelial cells. however, it has now emerged that amscs may predominantly act in a paracrine fashion and secreted exosomes. exosomes derived from amscs can result in changes to cell proliferation, migration and collagen synthesis, which can benefit wound healing. amscs-exosomes shorten the healing time and reduce scar formation of mouse skin incision wound. amscs-secreted exosomes can enter into the cytoplasm of fibroblasts. lipid raft-mediated endocytosis is responsible for exosomes uptake through erk1/2-heat shock protein 27 signaling in fibroblasts. besides, mirnas and proteins derived from exosomes mediate signal transduction in target cells following endocytosis, or membrane fusion.

Conclusion

exosome contents, after interval to cell, promote migration, proliferation and collagen secretion of fibroblasts. local injection of exosomes has also been reported to promote regeneration of damaged tissue. in vivo observations indicate that exosomes can be recruited to wound area via tail vein blood circulation, assembling around the wound on day 7 post-injection, aiding in the healing process. this phenomenon might be similar to the homing function of stem cells. it has been postulated that exosomes can avoid recognition/detection by the immune system, and maintain the integrity of cell membrane to avoid degradation. the injection of human amscs to mouse skin accelerates cutaneous wound healing in treated mice compared to control mice. interestingly, intravenous injection was superior at wound healing as compared to local injection and presumably loss of exosomes during local injection may contribute to this difference. in vivo studies showed that collagen i and iii distributions were promoted by exosomes in the early stage of wound healing, a result that was confirmed by with increased expressions of collagen i and iii. these results suggest that exosomes promote the early stages of wound healing by shortening healing time, while in the late stages, they might inhibit collagen synthesis to reduce scar formation. however, the specific mechanisms through which exosomes contribute to wound healing requires further investigation. in summary, the strong in vitro and in vitro evidence that amscs-exosome have promising potential for clinical application in soft tissue wound healing.

Keywords

Exosome, wound healing, stem cells