New therapeutic approaches of mesenchymal stem cells-derived exosomes (original) (raw)
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Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine
Journal of Translational Medicine
Mesenchymal stem cells (MSCs) have captured great attention in regenerative medicine for over a few decades by virtue of their differentiation capacity, potent immunomodulatory properties, and their ability to be favorably cultured and manipulated. Recent investigations implied that the pleiotropic effects of MSCs is not associated to their ability of differentiation, but rather is mediated by the secretion of soluble paracrine factors. Exosomes, nanoscale extracellular vesicles, are one of these paracrine mediators. Exosomes transfer functional cargos like miRNA and mRNA molecules, peptides, proteins, cytokines and lipids from MSCs to the recipient cells. Exosomes participate in intercellular communication events and contribute to the healing of injured or diseased tissues and organs. Studies reported that exosomes alone are responsible for the therapeutic effects of MSCs in numerous experimental models. Therefore, MSC-derived exosomes can be manipulated and applied to establish a ...
Life, 2021
Mesenchymal Stem Cells are potent therapeutic candidates in the field of regenerative medicine, owing to their immunomodulatory and differentiation potential. However, several complications come with their translational application like viability, duration, and degree of expansion, long-term storage, and high maintenance cost. Therefore, drawbacks of cell-based therapy can be overcome by a novel therapeutic modality emerging in translational research and application, i.e., exosomes. These small vesicles derived from mesenchymal stem cells are emerging as new avenues in the field of nano-medicine. These nano-vesicles have caught the attention of researchers with their potency as regenerative medicine both in nanotherapeutics and drug delivery systems. In this review, we discuss the current knowledge in the biology and handling of exosomes, with their limitations and future applications. Additionally, we highlight current perspectives that primarily focus on their effect on various di...
Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm
Biomarker Research, 2019
Mesenchymal stem/stromal cells (MSCs) have been demonstrated to hold great potential for the treatment of several diseases. Their therapeutic effects are largely mediated by paracrine factors including exosomes, which are nanometer-sized membrane-bound vesicles with functions as mediators of cell-cell communication. MSCderived exosomes contain cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. Increasing evidence suggests that MSC-derived exosomes might represent a novel cell-free therapy with compelling advantages over parent MSCs such as no risk of tumor formation and lower immunogenicity. This paper reviews the characteristics of MSC exosomes and their fate after in vivo administration, and highlights the therapeutic potential of MSC-derived exosomes in liver, kidney, cardiovascular and neurological disease. Particularly, we summarize the recent clinical trials performed to evaluate the safety and efficacy of MSC exosomes. Overall, this paper provides a general overview of MSCexosomes as a new cell-free therapeutic paradigm.
Mesenchymal stem cell-derived exosome: The likely game-changer in stem cell research
BIOCELL
Stem cell research is a promising area of transplantation and regenerative medicine with tremendous potential for improving the clinical treatment and diagnostic options across a variety of conditions and enhancing understanding of human development. Over the past few decades, mesenchymal stem cell (MSCs) studies have exponentially increased with a promising outcome. However, regardless of the huge investment and the research attention given to stem cell research, FDA approval for clinical use is still lacking. Amid the challenges confronting stem cell research as a cellbased product, there appears to be evidence of superior effect and heightened potential success in its expressed vesicles, exosomes, as cell-free products. In addition to their highly desirable intrinsic biologically unique structural, compositional, and morphological characteristics, as well as predominant physiochemical stability and biocompatibility properties, exosomes can also be altered to enhance their therapeutic capability or diagnostic imaging potential via physical, chemical, and biological modification approaches. More importantly, the powerful therapeutic potential and superior biological functions of exosomes, particularly, regarding engineered exosomes as cell-free products, and their utilization in a new generation of nanomedicine treatment, vaccination, and diagnosis platforms, brings hope of a change in the near future. This viewpoint discusses the trend of stem cell research and why stem cell-derived exosomes could be the game-changer.
Mesenchymal Cell-Derived Exosomes as Novel Useful Candidates for Drug Delivery
Archives of Neuroscience
Mesenchymal stem cells (MSCs) are one of the most accessible adult multipotent stem cells that can be harvested from various tissues. The tissue regeneration field uses MSCs because of their therapeutic potential in tissue damage repair, inflammation suppression, and anti-tumor therapies, relying on their targeted homing and differentiation capability into specialized cells. It is proposed that the paracrine activities of MSCs, including secretory trophic factors, survival signals, and extracellular vesicle release, are the principal mechanism to mediate MSCs function. Current studies show that exosomes secreted by MSCs may also contribute to MSCs' physiological function. Indeed, they can be introduced as hopeful novel candidates for drug delivery due to their nanoscale naturally-occurring structure, more stability, less immunogenicity, and the ability to pass through biological barriers without rejection to deliver their cargos to recipient cells and tissues. Moreover, exosomes may anticipate beneficial nanocarrier vehicles in targeted drug delivery systems.
Exosomes for drug delivery — a novel application for the mesenchymal stem cell
Biotechnology Advances, 2013
Exosomes are the most extensively characterized class of secreted membrane vesicles that carry proteins and RNAs for intercellular communication. They are increasingly seen as possible alternatives to liposomes as drug delivery vehicles. Like liposomes, they could deliver their cargo across the plasma membrane and provide a barrier against premature transformation and elimination. In addition, these naturally-occurring secreted membrane vesicles are less toxic and better tolerated in the body as evidenced by their ubiquitous presence in biological fluids, and have an intrinsic homing ability. They are also amenable to in vivo and in vitro loading of therapeutic agents, and membrane modifications to enhance tissue-specific homing. Here we propose human mesenchymal stem cells as the ideal cell source of exosomes for drug delivery. Mesenchymal stem cell transplantation for various disease indications has been extensively tested and shown to be safe in numerous clinical trials. These cells are also prolific producers of immunologically inert exosomes. Immortalization of these cells does not compromise the quantity or quality of exosome production, thus enabling infinite and reproducible exosome production from a single cell clone.
Preclinical translation of exosomes derived from mesenchymal stem/stromal cells
Preclinical Translation of Exosomes Derived from Mesenchymal Stem/Stromal Cells, 2019
Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the hori-zonal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there are over 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising , several outstanding questions remain to be answered that warrant further preclini-cal investigation.
Exosome: A Novel and Safer Therapeutic Refinement of Mesenchymal Stem Cell
Exosomes and Microvesicles, 2013
Mesenchymal stem cell (MSC) has just been approved as the first "off-the-shelf" stem cell pharmaceutical drug with an anticipation of more approvals following completion of numerous rigorous clinical trials. Despite this progress, the rationale for MSC therapeutic efficacy remains tenuous and is increasingly rationalized on a secretion rather than differentiation mechanism. Recent studies identifying exosome as the secreted agent mediating MSC therapeutic efficacy could potentially reduce a cell-based drug to a safer biologicbased alternative. Here we review the development of MSC exosome as a potential first-in-class therapeutic, and the unique challenges in the manufacture and regulatory oversight of this new class of therapeutics.
Mesenchymal Stem Cell-Derived Exosomes: New Opportunity in Cell-Free Therapy
Advanced Pharmaceutical Bulletin, 2016
Extracellular vesicles Extracellular vesicles (EVs) are a general term for different types of membranous components in the 20-1000 nm diameter which released by various cell types in cultured media include stem cells, B and T lymphocytes, dendritic cells, mast cells, adipocytes, neurons, platelets, endothelial and epithelial cells. 34-36 In addition, EVs isolated from many body fluids such as urine, serum, amniotic fluid, saliva, cerebrospinal fluid, breast milk, and nasal secretions. 37-41 Cancer cells secrete exosomes
Mesenchymal stem cell exosomes
Seminars in Cell & Developmental Biology, 2015
MSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical testing was based on their differentiation potential. However, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSCs exert their effects not through their differentiation potential but through their secreted product, more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes function as an extension of MSC's biological role as tissue stromal support cells. Like their cell source, MSC exosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biological processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis, enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesis provides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrum of diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiological functions and highlight some of their biochemical potential to illustrate how MSC exosomes could restore tissue homeostasis leading to tissue recovery and repair.