Osteoarthritis (OA) is the most common form of arthritis and is estimated to affect nearly 365 million people worldwide. Characterized as an inflammatory disease, OA slowly progresses over time and results in the gradual loss of the protective cartilage found on the ends of the bones.
While the specific cause of OA has yet to be determined, a growing body of evidence suggests the chondrocyte inflammatory response resulting from elevated levels of pro-inflammatory cytokines is a critical factor in the development and progression of OA.
Recent evidence also suggests that mesenchymal stem cell-derived exomes (MSCs-Exos) exhibit beneficial anti-inflammatory responses in several inflammatory diseases, including OA.
In this study, Wang et al. explore the role of human umbilical cord-derived MSCs-Exos (hUC-MSCs-Exos) in treating the inflammation of chondrocytes and its related mechanisms.
As part of this study, the authors report that supplementing the observed chondrocyte inflammation models with hUC-MSCs-Exos demonstrated the ability to reduce the inflammation of chondrocytes caused by the inflammatory factor IL-1β.
Additionally, activation and polarization of synovial macrophages to M1 phenotypes also contribute to the progression of OS. As part of this study, Wang et al. report that hUC-MSC-Exos demonstrated a protective effect against M1 macrophage-induced chondrocyte damage and cell death.
Wang et al. indicate that the results of this study confirm the anti-inflammatory effects of hUC-MSCs-Exos in the human articular chondrocytes inflammation model. The authors also conclude that hUC-MSCs-Exos may be used as a potential cell-free treatment for chondrocyte inflammation in OA.
Source: Wang S, Jiang W, Lv S, et al. Human umbilical cord mesenchymal stem cells-derived exosomes exert anti-inflammatory effects on osteoarthritis chondrocytes. Aging (Albany NY). 2023;15(18):9544-9560. doi:10.18632/aging.205034
According to the World Health Organization, at least 2.2 billion people worldwide have near or distant vision impairment. In at least 1 billion of these cases, vision impairment could have been prevented or has yet to be addressed. Glaucoma, corneal disease, and retinal disorders are among the leading contributors to these vision impairments.
Since the pathogenesis of these eye diseases is not fully understood, fully effective treatments have yet to be developed. Considering this, Li et al. reviewed recent research to examine the effectiveness of exosomes in various diseases in vivo, which provides the potential for a new option for the treatment of eye diseases.
Exosomes are extracellular small vesicles that are formed by the regulation of endocytosis, fusion, and efflux and contain a variety of biologically active substances, including proteins, miRNAs, IncRNAs, and lipids.
Exosomes are found in all biological fluids and have roles that vary depending on their origin. These roles include cell-to-cell communication, waste transfer, and regulation of the immune system in vivo. Additionally, when serving as a carrier, exosomes are involved in many pathological processes such as nerve repair, vascular regeneration, immune response, and fibrosis formation.
Examining the various roles exosomes play within the body, the authors of this review consider their role in the treatment of serious ocular diseases, including glaucoma, diabetic retinopathy, and keratitis. Li et al. point to studies demonstrating exosomes’ ability to promote the repair of injured nerves, inhibit fibrosis, modulate immune function, and promote angiogenesis as evidence of the important role they have in treating ocular disease.
Specifically, exosomes contain a large number of immunosuppressive molecules that inhibit lymphocyte proliferation and effectively increase ocular immune tolerance to prevent ocular autoimmune disease.
Exosomes can also transfer protein and RNA to receptor cells and can accelerate wound healing of corneal epithelial cells, providing a new approach for treating large corneal lesions.
Studies have also demonstrated a link between exosomes and age-related macular degeneration (AMD) with specific exosomes considered to have neuroprotective effects that are closely related to the pathological progression of AMD.
The authors conclude that exosomes are able to be used as therapeutic carriers to participate in processes such as immune response, angiogenesis, and nerve repair in ocular-related diseases. While research into this is still emerging, the presence and accessibility of exosomes will become a potential way to diagnose and treat ocular diseases.
Repairing the structure and functionality associated with subcutaneous cartilage defects continues to be a challenge in the fields of plastic and reconstructive surgery. While current methods, including autologous chondrocyte implantation and matrix-assisted chondrocyte implantation, have been successful in some regard, they continue to present a number of limitations, including donor limitation, donor morbidity, and degradation of the graft tissue.
Recently, cartilage progenitor cell (CPC)-based tissue engineering has drawn attention in the field of cartilage regeneration, primarily for its strong chondrogenic differentiation capacity.
Unfortunately, a general lack of a suitable chondrogenic niche has continued to hinder the clinical application of CPC-regenerated cartilage in the subcutaneous environment.
Considering this, and for the purposes of this study, Chen et al. explored the use of exosomes derived from chondrocytes (CC-Exos) as a way to provide the CPC constructs with a cartilage signal in subcutaneous environment for efficient ectopic cartilage regeneration.
After 12 weeks of post-surgical injection of CC-Exos, the authors’ animal model demonstrated that the CC-Exos injections effectively increased collagen deposition and minimized vascular ingrowth in engineered constructs, which efficiently and reproducibly developed into cartilage. This study also demonstrated that the CPC constructs supplied with these CC-Exos could also form cartilage-like tissue with minimal hypertrophy in a subcutaneous environment and with no help from any chondrogenic factors.
Additionally, Chen et al.’s study showed that CC-Exos significantly promoted chondrogenesis-related factors at the mRNA and protein levels in CPCs while also limiting angiogenesis typically associated with hypertrophic differentiation and subsequent calcification.
Despite these promising results, Chen et al. point out that the exact components associated with CC-Exos have yet to be determined. Because of this, the authors call for additional studies to determine the specific components of CC-Exos and their underlying mechanisms related to cartilage repair.
Considering the findings of this study, the authors believe that CC-Exos alone could provide a preferable chondrogenic environment, help maintain the stability of cartilage tissue, and serve as a promising therapeutic approach for the treatment of ectopic cartilage defects.
Source: Chen, Y., Xue, K., Zhang, X. et al. Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells. Stem Cell Res Ther 9, 318 (2018). https://doi.org/10.1186/s13287-018-1047-2
Osteoarthritis (OA) is a chronic joint condition that causes pain and lack of mobility through the progressive degradation of joint cartilage. While there are several current pharmaceutical, physical therapy, and surgical treatments to address the symptoms of OA, researchers are interested in developing new therapeutic treatment approaches to address the relentless progression of the condition.
Considering their documented biocompatibility, immunomodulatory properties, and ability to precisely target specific cells and tissues, exosomes have recently emerged as a promising therapeutic option as a drug delivery system (DDS) for the treatment of OA. Specifically, these exosome-based strategies have demonstrated a safe and effective way to enhance cartilage repair, mitigate inflammation, and alleviate the persistent pain associated with OA.
While the benefits of exosome-based DDSs have been demonstrated in numerous studies, according to the author of this review, the specific application of this option for the purpose of treating OA has not been sufficiently explored.
In this review, Lu et al. summarize the emerging developments surrounding exosome-based DDSs of OA and highlight the present challenges associated with this evolving therapeutic option.
Recent studies have demonstrated the benefit of using exosomes for the delivery of drugs designed to treat OA. Specifically, researchers have found that exosomes derived from mesenchymal stem cells (MSCs) are able to be effective carriers for the delivery of specific molecules that lead to the promotion of chondrogenesis and improvement in cartilage regeneration. These same exosomes have also demonstrated themselves to be effective carriers for the localized delivery of anti-inflammatory drugs known for their potent anti-inflammatory and immunosuppressive effects.
Other studies show the potential of exosomes as an effective way to deliver growth factors to the affected joint in a targeted and sustained manner. The same exosomes have also demonstrated promise as a platform for gene delivery to areas affected by OA; a few of the notable advantages include the ability to safeguard genetic material from degradation and enable targeted delivery to specific cells and tissues.
While there is seemingly unlimited potential for using exosomes as DDSs in OA treatment, Lu et al. also call attention to several technical challenges and limitations that need to be addressed in order to fully maximize their potential and to ensure their safe application. These challenges and limitations include figuring out how to obtain a consistent supply of high-quality exosomes, developing effective methods that allows for efficient loading and controlled release of therapeutic molecules within exosomes, and a current lack of comprehensive long-term data regarding the safety and biocompatibility of exosome-based therapies.
Despite these challenges and limitations, the authors conclude that exosomes have emerged as highly promising candidates for drug delivery in OA therapy and offer numerous advantages over conventional delivery systems.
Source: Jun Lu, Yan Zhang, Xinquan Yang, Hongmou Zhao, Harnessing exosomes as cutting-edge drug delivery systems for revolutionary osteoarthritis therapy, Biomedicine & Pharmacotherapy, Volume 165,2023,115135, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2023.115135.
Systemic lupus erythematosus (SLE) is a common multisystemic autoimmune disease that often results in multi-organ damage when left untreated. Currently affecting over 1.5 million Americans, the etiology and pathogenesis of SLE continue to remain unclear.
At present, glucocorticoids and immunosuppressants are the most prescribed course of therapeutic treatment and mostly as a way to manage and treat symptoms of SLE, not the cause itself.
Considering that the etiology and pathogenesis of SLE are accompanied by immune disorders including abnormal proliferation, differentiation, and activation and dysfunction of T cells, and that mesenchymal stem cells (MSC) and MSC-derived extracellular vesicles (EVs) play important roles in the immunity process, researchers are increasingly turning their attention to MSCs and EVs as potential therapeutic treatment options for SLE.
In this review, Yang et al. examine the immunomodulatory effects and related mechanisms of MSCs and EVs in SLE with hopes of better understanding SLE pathogenesis and guiding biological therapy.
Examining the potential use of MSC and MSC-EVs in SLE treatment the authors found some studies have established that MSCs reduce adverse effects of immunosuppressive drugs and when combined have demonstrated distinct effects on T cell activation and bias.
Additionally, Yang et al. report that MSCs are able to participate in the immune response in two distinct ways: paracrine effect and directly through cell-to-cell interaction. Since reconstruction of immune tolerance and tissue regeneration and repair are required parts of SLE treatment and since MSCs possess high self-renewal ability, rapid expansion in vitro and in vitro, and low immunogenicity, allogeneic MSC transplantation has demonstrated strong evidence for the therapeutic potential of MSC in SLE.
Besides the ability to repair and regenerate tissue, MSCs, and MSC-EVs have strong anti-inflammatory and immunomodulatory effects, making them a potentially ideal treatment option as part of a therapeutic strategy for SLE. Considering that MSC-EVs have similar biological functions with MSCs, but are also considered cell-free, the authors point out that MSC-EVs could be the better choice for SLE treatment in the future.
Despite the potential of MSC and MSC-EVs, Yang et al. point out that genetic modification, metabolic recombination, and other priming of MSCs in vitro should be considered before MSC/MSC-EVs application for SLE treatment. The authors also recommend further clinical evaluation of the time of infusion, appropriate dosage, interval of treatment, and long-term safety of MSC/MSC-EVs in the treatment of SLE before any form of the combination is used as a treatment option.
Cardiovascular diseases continue to be the leading cause of death globally, accounting for nearly 18 million deaths each year with heart attack and stroke accounting for 80% of deaths.
Recently, stem-cell-based therapy has demonstrated the potential to regenerate damaged myocardium and to treat a wide range of cardiovascular diseases (CVDs). Specifically, the ability of mesenchymal stem cells (MSCs) to differentiate into cardiomyocytes, endothelial cells, and vascular smooth muscle cells has created a potentially new and promising therapeutic approach for the treatment of CVDs.
Huang et al. summarize the recent advances in MSC therapy, including the role of exosomes in future treatments of CVDs.
Recent studies have demonstrated that MSCs were able to secret cholesterol-rich, phospholipid exomes that were enriched with microRNAs (miRNAs). These exomes are nano-sized particles originating from multivesicular endosomal ranging in size from 30 – 100 nm and contain cytokines, proteins, lipids, mRNAs, and miRNAs. These exosomes are suggested as central mediators of intercellular communication and transfer proteins, mRNAs and miRNAs to adjacent cells.
The miRNAs found in exosomes play an essential role in various physiological and pathological processes by regulating gene expression at the post-transcription level. When applied in the cardiovascular system, miRNAs are internalized into CMCs and ECs and result in cardiomyocyte protection and angiogenesis promotion that has demonstrated beneficial and anti-inflammatory effects including cardiac regeneration, neovascularization, and anti-vascular remodeling; these observed benefits include improved cardiac function after a myocardial infarction (MI), reduced inflammation related to pulmonary hypertension, and increased tissue healing following an ischemia-reperfusion injury.
Huang et al. conclude that the studies evaluated in this review provide evidence that MSC-derived exosomes play an essential role in MSC-based therapy of CVDs including MI, reperfusion injury, and PH. Considering these conclusions, the authors call for additional studies to determine the detailed mechanisms and underlying benefits to determine their exact role.
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