Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine – a new paradigm for tissue repair

2018 ◽  
Vol 6 (1) ◽  
pp. 60-78 ◽  
Author(s):  
I. M. Bjørge ◽  
S. Y. Kim ◽  
J. F. Mano ◽  
B. Kalionis ◽  
W. Chrzanowski
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
New Paradigm ◽  
Ribonucleic Acids ◽  
Biological Signals

Extracellular vesicles are highly specialized messengers that deliver vital biological signals including ribonucleic acids – key modulators in tissue regeneration.

Made by cells for cells – extracellular vesicles as next-generation mainstream medicines

2022 ◽  
Vol 135 (1) ◽  
Author(s):  
Thanh Huyen Phan ◽  
Sally Yunsun Kim ◽  
Christopher Rudge ◽  
Wojciech Chrzanowski
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Early Stage ◽  
High Sensitivity ◽  
Bone Tissue Regeneration ◽  
Target Cells ◽  
Disease Detection ◽  
Next Generation ◽  
Based Medicine

ABSTRACT Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles in Tissue Regeneration

2020 ◽  
Vol 29 ◽  
pp. 096368972090850 ◽  
Author(s):  
Bocheng Zhang ◽  
Xiaoyuan Tian ◽  
Jun Hao ◽  
Gang Xu ◽  
Weiguo Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Tissue Repair ◽  
Membrane Structure ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Self Renewal ◽  
Multipotent Stem Cells

Mesenchymal stem cells (MSCs) are multipotent stem cells that have attracted increasing interest in the field of regenerative medicine. Previously, the differentiation ability of MSCs was believed to be primarily responsible for tissue repair. Recent studies have shown that paracrine mechanisms play an important role in this process. MSCs can secrete soluble molecules and extracellular vesicles (EVs), which mediate paracrine communication. EVs contain large amounts of proteins and nucleic acids, such as mRNAs and microRNAs (miRNAs), and can transfer the cargo between cells. The cargoes are similar to those in MSCs and are not susceptible to degradation due to the protection of the EV bimolecular membrane structure. MSC-EVs can mimic the biological characteristics of MSCs, such as differentiation, maturation, and self-renewal. Due to their broad biological functions and their ability to transfer molecules between cells, EVs have been intensively studied by an increasing number of researchers with a focus on therapeutic applications, especially those of EVs secreted by MSCs. In this review, we discuss MSC-derived EVs and their therapeutic potential in tissue regeneration.

scholarly journals Engineering Extracellular Vesicles as Nanotherapeutics for Regenerative Medicine

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 48 ◽  
Author(s):  
Lalithasri Ramasubramanian ◽  
Priyadarsini Kumar ◽  
Aijun Wang
Keyword(s):  
Cell Proliferation ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Functional Heterogeneity ◽  
Isolation And Purification ◽  
Natural Properties ◽  
New Class ◽  
Matrix Organization ◽  
Recycled Waste

Long thought of to be vesicles that primarily recycled waste biomolecules from cells, extracellular vesicles (EVs) have now emerged as a new class of nanotherapeutics for regenerative medicine. Recent studies have proven their potential as mediators of cell proliferation, immunomodulation, extracellular matrix organization and angiogenesis, and are currently being used as treatments for a variety of diseases and injuries. They are now being used in combination with a variety of more traditional biomaterials and tissue engineering strategies to stimulate tissue repair and wound healing. However, the clinical translation of EVs has been greatly slowed due to difficulties in EV isolation and purification, as well as their limited yields and functional heterogeneity. Thus, a field of EV engineering has emerged in order to augment the natural properties of EVs and to recapitulate their function in semi-synthetic and synthetic EVs. Here, we have reviewed current technologies and techniques in this growing field of EV engineering while highlighting possible future applications for regenerative medicine.

scholarly journals Extracellular Vesicles in Musculoskeletal Regeneration: Modulating the Therapy of the Future

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 43
Author(s):  
Hugo Abreu ◽  
Elena Canciani ◽  
Davide Raineri ◽  
Giuseppe Cappellano ◽  
Lia Rimondini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Stromal Cells ◽  
Ethical Issues ◽  
Musculoskeletal Diseases ◽  
Cell Types ◽  
Health Sciences ◽  
Bone Homeostasis

Tissue regeneration is a hot topic in health sciences, particularly because effective therapies promoting the healing of several cell types are lacking, specifically those of the musculoskeletal system. Mesenchymal Stem/Stromal Cells (MSCs) have been identified as crucial players in bone homeostasis, and are considered a promising therapy for diseases such as osteoarthritis (OA) and Rheumatoid Arthritis (RA). However, some known drawbacks limit their use, particularly ethical issues and immunological rejections. Thus, MSCs byproducts, namely Extracellular Vesicles (EVs), are emerging as potential solutions to overcome some of the issues of the original cells. EVs can be modulated by either cellular preconditioning or vesicle engineering, and thus represent a plastic tool to be implemented in regenerative medicine. Further, the use of biomaterials is important to improve EV delivery and indirectly to modulate their content and secretion. This review aims to connect the dots among MSCs, EVs, and biomaterials, in the context of musculoskeletal diseases.

Effects of Extracellular Vesicles Derived from Mesenchymal Stem/Stromal Cells on Liver Diseases

2019 ◽  
Vol 14 (5) ◽  
pp. 442-452 ◽  
Author(s):  
Wenjie Zheng ◽  
Yumin Yang ◽  
Russel Clive Sequeira ◽  
Colin E. Bishop ◽  
Anthony Atala ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Liver Diseases ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Chronic Liver Injury ◽  
Mediated Effects ◽  
Therapeutic Benefits

Therapeutic effects of Mesenchymal Stem/Stromal Cells (MSCs) transplantation have been observed in various disease models. However, it is thought that MSCs-mediated effects largely depend on the paracrine manner of secreting cytokines, growth factors, and Extracellular Vesicles (EVs). Similarly, MSCs-derived EVs also showed therapeutic benefits in various liver diseases through alleviating fibrosis, improving regeneration of hepatocytes, and regulating immune activity. This review provides an overview of the MSCs, their EVs, and their therapeutic potential in treating various liver diseases including liver fibrosis, acute and chronic liver injury, and Hepatocellular Carcinoma (HCC). More specifically, the mechanisms by which MSC-EVs induce therapeutic benefits in liver diseases will be covered. In addition, comparisons between MSCs and their EVs were also evaluated as regenerative medicine against liver diseases. While the mechanisms of action and clinical efficacy must continue to be evaluated and verified, MSCs-derived EVs currently show tremendous potential and promise as a regenerative medicine treatment for liver disease in the future.

scholarly journals Cell-free Exosome-laden Scaffolds for Tissue Repair

Nanoscale ◽  
2021 ◽  
Author(s):  
Jianghong Huang ◽  
Jianyi Xiong ◽  
Lei Yang ◽  
Jun Zhang ◽  
Shuqing Sun ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Tissue Repair ◽  
Cellular Tissue ◽  
The Core ◽  
Organ Level

With the development of regenerative medicine, tissue repair at the molecular, cellular, tissue, and organ level has seen continuous improvements over traditional techniques. As the core of tissue repair, seed...

scholarly journals Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1872
Author(s):  
Shaowei Guo ◽  
Idan Redenski ◽  
Shulamit Levenberg
Keyword(s):  
Spinal Cord ◽  
Tissue Engineering ◽  
Extracellular Vesicles ◽  
Functional Recovery ◽  
Three Dimensional ◽  
Therapeutic Modality ◽  
Spinal Cord Tissue ◽  
New Paradigm ◽  
Cord Injury ◽  
Severe Motor

Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting “cell-free” therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals NANOmetric BIO-Banked MSC-Derived Exosome (NANOBIOME) as a Novel Approach to Regenerative Medicine

2018 ◽  
Vol 7 (10) ◽  
pp. 357 ◽  
Author(s):  
Bruna Codispoti ◽  
Massimo Marrelli ◽  
Francesco Paduano ◽  
Marco Tatullo
Keyword(s):  
Plasma Membrane ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Cell Types ◽  
Endogenous Factors ◽  
Cell Lineages ◽  
Novel Approach ◽  
Therapeutic Uses ◽  
Technical Issues

Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. In fact, MSCs can differentiate into several cell lineages and show paracrine behavior by releasing endogenous factors that stimulate tissue repair and modulate local immune response. Each MSC type is affected by specific biobanking issues—technical issues as well as regulatory and ethical concerns—thus making it quite tricky to safely and commonly use MSC banking for swift regenerative applications. Extracellular vesicles (EVs) include a group of 150–1000 nm vesicles that are released by budding from the plasma membrane into biological fluids and/or in the culture medium from varied and heterogenic cell types. EVs consist of various vesicle types that are defined with different nomenclature such as exosomes, shedding vesicles, nanoparticles, microvesicles and apoptotic bodies. Ectosomes, micro- and nanoparticles generally refer to the direct release of single vesicles from the plasma membrane. While many studies describe exosomes as deriving from multivesicular bodies, solid evidence about the origin of EVs is often lacking. Extracellular vesicles represent an important portion of the cell secretome. Their numerous properties can be used for diagnostic, prognostic, and therapeutic uses, so EVs are considered to be innovative and smart theranostic tools. The aim of this review is to investigate the usefulness of exosomes as carriers of the whole information panel characterizing the use of MSCs in regenerative medicine. Our purpose is to make a step forward in the development of the NANOmetric BIO-banked MSC-derived Exosome (NANOBIOME).

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