Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach

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Abstract

Extracellular vesicles (EVs) are a newly-discovered way by which cells communicate with their neighbors, as well as transporting cargos which once were considered to be limited by membrane barriers, including membrane proteins, cytosolic proteins and RNA. The discovery of platelet-derived EVs (P-EVs), the most abundant EVs in human blood, has been a very tortuous process. At first, P-EVs were identified as nothing but 'platelet dust', and subsequent research did not progress smoothly because of the limited research techniques to study EVs. Following leaps and bounds of technical progress in studying EVs, more and more attractive features of P-EVs were revealed and they began to be further researched. The aim of this review is to present the latest knowledge about the role of P-EVs in tissue repair and tumor progression. The potential mechanism of P-EVs is emphasized. Then the limitations of the present study and future research directions are discussed.

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Most cited references 49

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Trousseau's syndrome: multiple definitions and multiple mechanisms.

Ajit Varki (2007)

In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.

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Extracellular vesicles shuffling intercellular messages: for good or for bad.

Alessandra Lo Cicero, Philip Stahl, Graça Raposo (2015)

The release of extracellular vesicles (EVs) is a highly conserved process exploited by diverse organisms as a mode of intercellular communication. Vesicles of sizes ranging from 30 to 1000nm, or even larger, are generated by blebbing of the plasma membrane (microvesicles) or formed in multivesicular endosomes (MVEs) to be secreted by exocytosis as exosomes. Exosomes, microvesicles and other EVs contain membrane and cytosolic components that include proteins, lipids and RNAs, a composition that differs related to their site of biogenesis. Several mechanisms are involved in vesicle formation at the plasma membrane or in endosomes, which is reflected in their heterogeneity, size and composition. EVs have significant promise for therapeutics and diagnostics and for understanding physiological and pathological processes all of which have boosted research to find modulators of their composition, secretion and targeting.

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Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

Shang-chun Guo, Shi-Cong Tao, Wen-Jing Yin … (2017)

Chronic wounds have become an economic, social, and public health burden and need advanced treatment. Platelet-rich plasma (PRP) has been used extensively in treatment of chronic wounds because it contains an abundance of growth factors secreted by platelets. The exosomes derived from PRP (PRP-Exos) have been proven to encapsulate principal growth factors from platelets. This study is the first to show that these exosomes may exert the function of PRP. PRP-Exos can effectively induce proliferation and migration of endothelial cells and fibroblasts to improve angiogenesis and re-epithelialization in chronic wounds. We regulated YAP to verify the PRP-Exos-dependent effect on fibroblast proliferation and migration through YAP activation. In vivo, we observed the cutaneous healing process in chronic wounds treated with PRP-Exos in a diabetic rat model. We provide evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Biol Sci

Journal ID (iso-abbrev): Int. J. Biol. Sci

Journal ID (publisher-id): ijbs

Title: International Journal of Biological Sciences

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1449-2288

Publication date Collection: 2017

Publication date (Electronic): 6 July 2017

Volume: 13

Issue: 7

Pages: 828-834

Affiliations

[1 ]Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China;

[2 ]Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.

Author notes

✉ Corresponding authors: Chang-Qing Zhang, Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. E-mail: zhangcq@ 123456sjtu.edu.cn Shang-Chun Guo, Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China. E-mail: achuni@ 123456126.com

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: ijbsv13p0828

DOI: 10.7150/ijbs.19776

PMC ID: 5555101

PubMed ID: 28808416

SO-VID: 52bf7601-ee71-4ea6-a11f-44554a2a4f80

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This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach

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Bacterial extracellular vesicles

Most cited references 49

Trousseau's syndrome: multiple definitions and multiple mechanisms.

Extracellular vesicles shuffling intercellular messages: for good or for bad.

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

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