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 On the Choice of the Extracellular Vesicles for Therapeutic Purposes

2019 ◽  
Vol 20 (2) ◽  
pp. 236 ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Mariantonia Logozzi ◽  
Antonella Marino Gammazza ◽  
Davide Mizzoni ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Free Form ◽  
Target Cells ◽  
Disease Biomarkers ◽  
Cellular Source ◽  
Therapeutic Molecules

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of disease biomarkers and have high potential benefits in regenerative medicine. Indeed, they deliver both chemical and bio-molecules in a way that within exosomes drugs are more effective that in their exosome-free form. Thus, to date, we know that exosomes are shuttle disease biomarkers and probably the most effective way to deliver therapeutic molecules within target cells. However, we do not know exactly which exosomes may be used in therapy in avoiding side effects as well. In regenerative medicine, it will be ideal to use autologous exosomes, but it seems not ideal to use plasma-derived exosomes, as they may contain potentially dangerous molecules. Here, we want to present and discuss a contradictory relatively unmet issue that is the lack of a general agreement on the choice for the source of extracellular vesicles for therapeutic use.

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.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Multipotent Cells ◽  
Membrane Bound

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

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 Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

2019 ◽  
Vol 20 (20) ◽  
pp. 4987 ◽  
Author(s):  
Oriana Trubiani ◽  
Guya D. Marconi ◽  
Sante D. Pierdomenico ◽  
Adriano Piattelli ◽  
Francesca Diomede ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Tissue ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
De Novo ◽  
Bone Tissue Regeneration ◽  
Growth Strategies ◽  
Biomaterial Scaffold ◽  
Oral Stem Cells

Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

scholarly journals Mesenchymal Stromal Cell-Derived Extracellular Vesicles Regulate the Mitochondrial Metabolism via Transfer of miRNAs

2021 ◽  
Vol 12 ◽  
Author(s):  
Claire Loussouarn ◽  
Yves-Marie Pers ◽  
Claire Bony ◽  
Christian Jorgensen ◽  
Danièle Noël
Keyword(s):  
Energy Metabolism ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Mesenchymal Stromal Cell ◽  
Tissue Repair ◽  
Stromal Cell ◽  
Target Cells ◽  
Different Types ◽  
And Oxidative Stress

Mesenchymal stromal cells (MSCs) are the most commonly tested adult progenitor cells in regenerative medicine. They stimulate tissue repair primarily through the secretion of immune-regulatory and pro-regenerative factors. There is increasing evidence that most of these factors are carried on extracellular vesicles (EVs) that are released by MSCs, either spontaneously or after activation. Exosomes and microvesicles are the most investigated types of EVs that act through uptake by target cells and cargo release inside the cytoplasm or through interactions with receptors expressed on target cells to stimulate downstream intracellular pathways. They convey different types of molecules, including proteins, lipids and acid nucleics among which, miRNAs are the most widely studied. The cargo of EVs can be impacted by the culture or environmental conditions that MSCs encounter and by changes in the energy metabolism that regulate the functional properties of MSCs. On the other hand, MSC-derived EVs are also reported to impact the metabolism of target cells. In the present review, we discuss the role of MSC-EVs in the regulation of the energy metabolism and oxidative stress of target cells and tissues with a focus on the role of miRNAs.

Chitosan-Nanocellulose Composites for Regenerative Medicine Applications

2020 ◽  
Vol 27 (28) ◽  
pp. 4584-4592 ◽  
Author(s):  
Avik Khan ◽  
Baobin Wang ◽  
Yonghao Ni
Keyword(s):  
Regenerative Medicine ◽  
Preparation Method ◽  
Chemical Properties ◽  
Biological Properties ◽  
Next Generation ◽  
Structure Property ◽  
Physico Chemical ◽  
Structure Property Relationship ◽  
Attractive Candidate ◽  
Fundamental Understanding

Regenerative medicine represents an emerging multidisciplinary field that brings together engineering methods and complexity of life sciences into a unified fundamental understanding of structure-property relationship in micro/nano environment to develop the next generation of scaffolds and hydrogels to restore or improve tissue functions. Chitosan has several unique physico-chemical properties that make it a highly desirable polysaccharide for various applications such as, biomedical, food, nutraceutical, agriculture, packaging, coating, etc. However, the utilization of chitosan in regenerative medicine is often limited due to its inadequate mechanical, barrier and thermal properties. Cellulosic nanomaterials (CNs), owing to their exceptional mechanical strength, ease of chemical modification, biocompatibility and favorable interaction with chitosan, represent an attractive candidate for the fabrication of chitosan/ CNs scaffolds and hydrogels. The unique mechanical and biological properties of the chitosan/CNs bio-nanocomposite make them a material of choice for the development of next generation bio-scaffolds and hydrogels for regenerative medicine applications. In this review, we have summarized the preparation method, mechanical properties, morphology, cytotoxicity/ biocompatibility of chitosan/CNs nanocomposites for regenerative medicine applications, which comprises tissue engineering and wound dressing applications.

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.

A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next- Generation Sequencing

2020 ◽  
Vol 15 ◽  
Author(s):  
Zheng Jiang ◽  
Hui Liu ◽  
Siwen Zhang ◽  
Jia Liu ◽  
Weitao Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Microsatellite Instability ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
High Sensitivity ◽  
Next Generation ◽  
Tissue Samples ◽  
Next Generation Sequencing Technology ◽  
Medication Selection ◽  
Generation Sequencing

Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy. Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable. Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively. Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

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...

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