Therapeutic Applications Of Exosomes Research Articles

Evolving Role of Exosomes in Plastic and Reconstructive Surgery and Dermatology.

Exosomes, or extracellular vesicles, represent the latest cell-free addition to the regenerative medicine toolkit. In vitro preclinical studies have demonstrated the safety and efficacy of exosomes, which vary based on source and biomanufacturing, for a myriad of potential therapeutic applications relevant to skin and soft tissue reconstruction. Primary search was performed in September 2021 on the MEDLINE database via PubMed and Ovid, with focus on articles about therapeutic application of exosomes or extracellular vesicles. In total, 130 articles met criteria for applicability, including early-stage clinical trials, preclinical research studies with in vivo application, and articles applicable to plastic and reconstructive surgery and dermatology. Most studies used animal models of human disease processes, using either animal donor cells to isolate exosomes, or human donor cells in animal models. Exosome technology has catapulted as an acellular therapeutic vehicle with off-the-shelf accessibility. These features eliminate prior threshold for broad adoption of regenerative cell-based therapies into surgical and medical practice. To date, there are no exosome products approved by the US Food and Drug Administration. This review highlights exosomes as the new frontier in regenerative medicine and outlines its preclinical therapeutic applications for cutaneous repair and restoration.

Stem Cell-Based Acellular Therapy: Insight into Biogenesis, Bioengineering and Therapeutic Applications of Exosomes.

The vast regenerative potential of stem cells has laid the foundation for stem cell-based therapies. However, certain challenges limit the application of cell-based therapies. The therapeutic use of cell-free therapy can avoid limitations associated with cell-based therapies. Acellular stem cell-based therapies rely on the use of biological factors released by stem cells, including growth factors and extracellular vesicles such as exosomes. Due to their comparable regenerative potential, acellular therapies may provide a feasible and scalable alternative to stem cell-based therapies. Exosomes are small vesicles secreted by various types of cells, including stem cells. Exosomes contain parent cell-derived nucleic acids, proteins, lipids, and other bioactive molecules. They play an important role in intra-cellular communication and influence the biological characteristics of cells. Exosomes inherit the properties of their parent cells; therefore, stem cell-derived exosomes are of particular interest for applications of regenerative medicine. In comparison to stem cell-based therapy, exosome therapy offers several benefits, such as easy transport and storage, no risk of immunological rejection, and few ethical dilemmas. Unlike stem cells, exosomes can be lyophilized and stored off-the-shelf, making acellular therapies standardized and more accessible while reducing overall treatment costs. Exosome-based acellular treatments are therefore readily available for applications in patients at the time of care. The current review discusses the use of exosomes as an acellular therapy. The review explores the molecular mechanism of exosome biogenesis, various methods for exosome isolation, and characterization. In addition, the latest advancements in bioengineering techniques to enhance exosome potential for acellular therapies have been discussed. The challenges in the use of exosomes as well as their diverse applications for the diagnosis and treatment of diseases have been reviewed in detail.

Exosomes: Methods for Isolation and Characterization in Biological Samples.

Exosomes are small lipid bilayer-encapsulated nanosized extracellular vesicles of endosomal origin. Exosomes are secreted by almost all cell types and are a crucial player in intercellular communication. Exosomes transmit cellular information from donor to recipient cells in the form of proteins, lipids, and nucleic acids and influence several physiological and pathological responses. Due to their capacity to carry a variety of cellular cargo, low immunogenicity and cytotoxicity, biocompatibility, and ability to cross the blood-brain barrier, these nanosized vesicles are considered excellent diagnostic tools and drug-delivery vehicles. Despite their tremendous potential, the progress in therapeutic applications of exosomes is hindered by inadequate isolation techniques, poor characterization, and scarcity of specific biomarkers. The current research in the field is focused on overcoming these limitations. In this chapter, we have reviewed conventional exosome isolation and characterization methods and recent advancements, their advantages and limitations, persistent challenges in exosome research, and future directions.

Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics.

In the era of precision medicine, liquid biopsy techniques, especially the use of urine analysis, represent a paradigm shift in the identification of biomarkers, with considerable implications for clinical practice in the field of nephrology. In kidney diseases, the use of this non-invasive tool to identify specific and sensitive biomarkers other than plasma creatinine and the glomerular filtration rate is becoming crucial for the diagnosis and assessment of a patient's condition. In recent years, studies have drawn attention to the importance of exosomes for diagnostic and therapeutic purposes in kidney diseases. Exosomes are nano-sized extracellular vesicles with a lipid bilayer structure, composed of a variety of biologically active substances. In the context of kidney diseases, studies have demonstrated that exosomes are valuable carriers of information and are delivery vectors, rendering them appealing candidates as biomarkers and drug delivery vehicles with beneficial therapeutic outcomes for kidney diseases. This review summarizes the applications of exosomes in kidney diseases, emphasizing the current biomarkers of renal diseases identified from urinary exosomes and the therapeutic applications of exosomes with reference to drug delivery and immunomodulation. Finally, we discuss the challenges encountered when using exosomes for therapeutic purposes and how these may affect its clinical applications.

Various Three-Dimensional Culture Methods and Cell Types for Exosome Production.

Cell-based therapies have been used as promising treatments for several untreatable diseases. However, cell-based therapies have side effects such as tumorigenesis and immune responses. To overcome these side effects, therapeutic effects of exosomes have been researched as replacements for cell-based therapies. In addition, exosomes reduced the risk that can be induced by cell-based therapies. Exosomes contain biomolecules such as proteins, lipids, and nucleic acids that play an essential role in cell-cell and cell-matrix interactions during biological processes. Since the introduction of exosomes, those have been proven perpetually as one of the most effective and therapeutic methods for incurable diseases. Much research has been conducted to enhance the properties of exosomes, including immune regulation, tissue repair, and regeneration. However, yield rate of exosomes is the critical obstacle that should be overcome for practical cell-free therapy. Three-dimensional (3D) culture methods are introduced as a breakthrough to get higher production yields of exosomes. For example, hanging drop and microwell were well known 3D culture methods and easy to use without invasiveness. However, these methods have limitation in mass production of exosomes. Therefore, a scaffold, spinner flask, and fiber bioreactor were introduced for mass production of exosomes isolated from various cell types. Furthermore, exosomes treatments derived from 3D cultured cells showed enhanced cell proliferation, angiogenesis, and immunosuppressive properties. This review provides therapeutic applications of exosomes using 3D culture methods.

Exosomes and ultrasound: The future of theranostic applications.

Biomaterials and pertaining formulations have been very successful in various diagnostic and therapeutic applications because of its ability to overcome pharmacological limitations. Some of them have gained significant focus in the recent decade for their theranostic properties. Exosomes can be grouped as biomaterials, since they consist of various biological micro/macromolecules and possess all the properties of a stable biomaterial with size in nano range. Significant research has gone into isolation and exploitation of exosomes as potential theranostic agent. However, the limitations in terms of yield, efficacy, and target specificity are continuously being addressed. On the other hand, several nano/microformulations are responsive to physical or chemical alterations and were successfully stimulated by tweaking the physical characteristics of the surrounding environment they are in. Some of them are termed as photodynamic, sonodynamic or thermodynamic therapeutic systems. In this regard, ultrasound and acoustic systems were extensively studied for its ability towards altering the properties of the systems to which they were applied on. In this review, we have detailed about the diagnostic and therapeutic applications of exosomes and ultrasound separately, consisting of their conventional applications, drawbacks, and developments for addressing the challenges. The information were categorized into various sections that provide complete overview of the isolation strategies and theranostic applications of exosomes in various diseases. Then the ultrasound-based disease diagnosis and therapy were elaborated, with special interest towards the use of ultrasound in enhancing the efficacy of nanomedicines and nanodrug delivery systems, Finally, we discussed about the ability of ultrasound in enhancing the diagnostic and therapeutic properties of exosomes, which could be the future of theranostics.

The role and therapeutic applications of exosomes in multiple sclerosis disease.

A range of the central nervous system (CNS) and immune cells are affected by multiple sclerosis (MS), a complex autoimmune disease of the CNS. Chronic neuroinflammation, demyelination, and neuronal death are all features of MS, but the disease's molecular mechanisms are unknown. Exosomes are small, membrane-bound extracellular vesicles with a crucial role in cell communication. They are stable in biological fluids and emerge from the cell membrane during endocytic internalization. It might be possible to recognize better the mechanisms involved in the development and progress of illnesses by understanding the variety of exosomal contents and their associated targets, like neurologic disorders. In this review, we sought to bring together important data on the biology of exosomes in MS and highlight discoveries on these nanoparticles' prognostic, diagnostic and therapeutic potential.

Chemical Advances in Therapeutic Application of Exosomes and Liposomes.

Exosomes and liposomes are vesicular nanoparticles that can encapsulate functional cargo. The chemical similarities between naturally occurring exosomes and synthetic liposomes have accelerated the development of exosome mimetics as a therapeutic drug delivery platform under physiological and pathological environments. To maximise the applications of exosomes and liposomes in the clinical setting, it is essential to look into their basic chemical properties and utilise these characteristics to optimise the preparation, loading, modification and hybridisation. This review summarises the chemical and biological properties of both exosomal and liposomal systems as well as some of the challenges related to their production and application. This article concludes with a discussion on potential perspectives for the integration of exosomal and liposomal technologies in mapping better approaches for their biomedical use, especially in therapeutics.

Regeneration and Diagnosis of Kidney Disease Using Exosomes

: A growing global prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD), high costs of kidney transplantation, a shortage of kidney donors, and low survival rate after dialysis have popularized mesenchymal stem cell (MSC) therapy via transplantation. However, the risks of tumorigenesis, immune rejection, pathogen transmission, loss of differentiation, and morphological changes after long-term culture have prompted researchers to develop a safer and more effective therapy method. Therefore, cell-free approaches have been developed to reduce the risks associated with stem cell-based therapies. In cell-free therapy of AKI and CKD, MSC-derived extracellular vesicles, with nanometer sizes, are used, called exosomes. Exosomes have a lipid bilayer membrane with various genes, microRNAs, and proteins for kidney repair. As known, MSC-derived exosomes have improved the kidney regeneration process for various reasons, such as increased safety and reduced inflammation, immune rejection, and tumorigenesis. With the advancement of exosome isolation techniques, the possibility of using biologically active molecules for renal injury prediction and diagnosis has emerged. The use of urinary exosomes in AKI and CKD diagnosis is based on changes in the expression of specific molecule cargos of exosomes. This review article summarizes the diagnosis and therapeutic applications of exosomes in AKI and CKD.

Exosomes: A Friend or Foe for Osteoporotic Fracture?

The clinical need for effective osteoporotic fracture therapy and prevention remains urgent. The occurrence and healing of osteoporotic fracture are closely associated with the continuous processes of bone modeling, remodeling, and regeneration. Accumulating evidence has indicated a prominent role of exosomes in mediating multiple pathophysiological processes, which are essential for information and materials exchange and exerting pleiotropic effects on neighboring or distant bone-related cells. Therefore, the exosomes are considered as important candidates both in the occurrence and healing of osteoporotic fracture by accelerating or suppressing related processes. In this review, we collectively focused on recent findings on the diagnostic and therapeutic applications of exosomes in osteoporotic fracture by regulating osteoblastogenesis, osteoclastogenesis, and angiogenesis, providing us with novel therapeutic strategies for osteoporotic fracture in clinical practice.

The Significance of Exosomal RNAs in the Development, Diagnosis, and Treatment of Gastric Cancer.

Gastric cancer (GC) is one of the most common malignancies in the world. Exosomes, a subset of extracellular vesicles with an average diameter of 100 nm, contain and transfer a variety of functional macromolecules such as proteins, lipids, and nucleic acids. A large number of studies indicated that exosomes can play a significant role in the initiation and development of GC via facilitating intercellular communication between gastric cancer cells and microenvironment. Exosomal RNAs, one of the key functional cargos, are involved in the pathogenesis, development, and metastasis of GC. In addition, recent studies elucidated that exosomal RNAs may serve as diagnostic and prognostic biomarkers or therapeutic targets for GC. In this review, we summarized the function of exosomal RNA in the tumorigenesis, progression, diagnosis, and treatment of GC, which may further unveil the functions of exosome and promote the potentially diagnostic and therapeutic application of exosomes in GC.

The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review

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An Overview of Exosomes in Cancer Therapy: A Small Solution to a Big Problem

Exosomes are defined as a type of extracellular vesicle released when multivesicular bodies of the endocytic pathway fuse with the plasma membrane. They are characterized by their role in extracellular communication, partly due to their composition, and present the ability to recognize and interact with cells from the immune system, enabling an immune response. Their targeting capability and nanosized dimensions make them great candidates for cancer therapy. As chemotherapy is associated with cytotoxicity and multiple drug resistance, the use of exosomes targeting capabilities, able to deliver anticancer drugs specifically to cancer cells, is a great approach to overcome these disadvantages. The objective is to assess treatment efficiency in reducing tumor cells, as well as overall safety and response by cancer carriers. So far, results show exosomes as a promising therapeutic strategy in the fight against cancer. This review summarizes the characteristics and composition of exosomes, as well as explaining in detail the involved parties in the origin of exosomes. Furthermore, some considerations about exosome application in immunotherapy are addressed. The main isolation and loading methods are described to give an insight into how exosomes can be obtained and manipulated. Finally, some therapeutic applications of exosomes in cancer therapy are described.

The Potential of Milk-Derived Exosomes for Drug Delivery.

Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Due to their hydrophobic lipid bilayer and aqueous hydrophilic core structure, they are considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, but they are also less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited. A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery. Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced. The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.

Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC).

Exosomes are nanovesicles part of a recently described intercellular communication system. Their properties seem promising as a biomarker in cancer research, where more sensitive monitoring and therapeutic applications are desperately needed. In the case of head and neck squamous cell carcinoma (HNSCC), overall survival often remains poor, although huge technological advancements in the treatment of this disease have been made. In the following review, diagnostic and therapeutic properties are highlighted and summarised. Impressive first results have been obtained but more research is needed to implement these innovative techniques into daily clinical routines.

Exosomes in Ischemic Stroke.

Ischemic stroke, a leading cause of mortality, results in severe neurological outcomes in the patients. Effective stroke therapies may significantly decrease the extent of injury. For this purpose, novel and efficient drug delivery strategies need to be developed. Among a myriad of therapeutic and drug delivery techniques, exosomes have shown promising results in ischemic stroke either by their intrinsic therapeutic characteristics, which can result in angiogenesis and neurogenesis or by acting as competent, biocompatible drug delivery vehicles to transport neurotherapeutic agents into the brain. In this review, we have discussed different methods of exosome isolation and cargo loading techniques, advantages and disadvantages of using exosomes as a drug delivery carrier and the therapeutic applications of exosomes with a focus on ischemic stroke therapy.

The Therapeutic Applications of Exosomes in Different Types of Diseases: A Review.

Exosomes are nano-sized vesicles secreted by nearly all cells and have received massive attention recently. In addition to their roles in pathophysiological processes and diagnostic evaluations, recently, several studies have applied exosomes to design novel therapeutic applications. Exosomes can be derived from a variety of cells and tissues and based on the source, they can carry different native contents such as DNAs, non-coding small RNAs, mRNAs, and proteins. They can also be engineered by adding desirable agents including specific biomolecules or drugs. Both forms can be therapeutically used for delivering their cargoes to the target cells and desirably alter their functions. The present study aimed to provide a comprehensive review of the various studies which applied exosomes as a therapeutic tool in the treatment of different types of diseases including cancer, cardiovascular, neurologic, psychiatric, liver, and kidney diseases.

Roles and Functions of Exosomal Non-coding RNAs in Vascular Aging.

Aging is a progressive loss of physiological integrity and functionality process which increases susceptibility and mortality to diseases. Vascular aging is a specific type of organic aging. The structure and function changes of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cause of vascular aging, which could influence the threshold, process, and severity of vascular related diseases. Accumulating evidences demonstrate that exosomes serve as novel intercellular information communicator between cell to cell by delivering variety biologically active cargos, especially exosomal non-coding RNAs (ncRNAs), which are associated with most of aging-related biological and functional disorders. In this review, we will summerize the emerging roles and mechanisms of exosomal ncRNAs in vascular aging and vascular aging related diseases, focusing on the role of exosomal miRNAs and lncRNAs in regulating the functions of ECs and VSMCs. Moreover, the relationship between the ECs and VSMCs linked by exosomes, the potential diagnostic and therapeutic application of exosomes in vascular aging and the clinical evaluation and treatment of vascular aging and vascular aging related diseases will also be discussed.

Exosomes: New insights into cancer mechanisms.

Exosomes are mobile extracellular vesicles with a diameter 40 to 150 nm. They play a critical role in several processes such as the development of cancers, intercellular signaling, drug resistance mechanisms, and cell-to-cell communication by fusion onto the cell membrane ofrecipient cells. These vesicles contain endogenous proteins and both noncoding and coding RNAs (microRNAand messenger RNAs) that can be delivered to various types of cells. Furthermore, exosomes exist in body fluids such as plasma, cerebrospinal fluid, and urine. Therefore, they could be used as a novel carrier to deliver therapeutic nucleic-acid drugs for cancer therapy. It was recently documented that, hypoxia promotes exosomes secretion in different tumor types leading to the activation of vascular cells and angiogenesis. Cancer cell-derived exosomes (CCEs) have been used as prognostic and diagnostic markers in many types of cancers because exosomes are stable at 4°Cand -70°C. CCEs have many functional roles in tumorigenesis, metastasis, and invasion. Consequently, this review presents the data about the therapeutic application of exosomes and the role of CCEs in cancer invasion, drug resistance, and metastasis.

Role of the Exosome in Ovarian Cancer Progression and Its Potential as a Therapeutic Target.

Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30–150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and lipids. Furthermore, therapeutic applications of exosomes as drug cargo delivery are attracting research interest because exosomes are stabilized in circulation. This review highlights the functions of exosomes in each process of the peritoneal dissemination of ovarian cancer and discusses their potential for cancer therapeutics.