Exosome-based therapies for inflammatory disorders: a review of recent advances.

Exosomes, small extracellular vesicles secreted by cells, have emerged as focal mediators in intercellular communication and therapeutic interventions across diverse biomedical fields. Inflammatory disorders, including inflammatory bowel disease, acute liver injury, lung injury, neuroinflammation, and myocardial infarction, are complex conditions that require innovative therapeutic approaches. This review summarizes recent advances in exosome-based therapies for inflammatory disorders, highlighting their potential as diagnostic biomarkers and therapeutic agents.

Immunomodulatory effect of mesenchymal stem cells-derived extracellular vesicles to modulate the regulatory T cells and Th1/Th2 imbalance in peripheral blood mononuclear cells of patients with allergic rhinitis.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising immunomodulatory capabilities for a variety of clinical conditions. However, the potential regulatory mechanisms of MSC-EVs in allergic rhinitis (AR) remain unexplored. The present study was designed to investigate the immunomodulatory effect of MSC-EVs in patients with AR.

Signaling pathways activated and regulated by stem cell-derived exosome therapy.

Stem cell-derived exosomes exert comparable therapeutic effects to those of their parental stem cells without causing immunogenic, tumorigenic, and ethical disadvantages. Their therapeutic advantages are manifested in the management of a broad spectrum of diseases, and their dosing versatility are exemplified by systemic administration and local delivery. Furthermore, the activation and regulation of various signaling cascades have provided foundation for the claimed curative effects of exosomal therapy.

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis.

Introduction: Allergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases.

Local Delivery of Dual Stem Cell-Derived Exosomes Using an Electrospun Nanofibrous Platform for the Treatment of Traumatic Brain Injury.

Traumatic brain injury poses serious physical, psychosocial, and economic threats. Although systemic administration of stem cell-derived exosomes has recently been proven to be a promising modality for traumatic brain injury treatment, they come with distinct drawbacks. Luckily, various biomaterials have been developed to assist local delivery of exosomes to improve the targeting of organs, minimize nonspecific accumulation in vital organs, and ensure the protection and release of exosomes.

Evaluating the potential of Abelmoschus esculentus, Solanum melongena, and Capsicum annuum spp. for nutrient and microbial reduction from wastewater in hybrid constructed wetland.

Utilizing engineered wetlands for the cultivation of vegetables can help to overcome the problems of water and food scarcity. These wetlands are primarily designed for wastewater treatment, and their efficiency and effectiveness can be improved by selecting an appropriate substrate. To investigate the potential for nutrient and microbial removal, the Abelmoschus esculentus, Solanum melongena, and Capsicum annuum L.

GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways.

Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs.

Clinical applications of stem cell-derived exosomes.

Although stem cell-based therapy has demonstrated considerable potential to manage certain diseases more successfully than conventional surgery, it nevertheless comes with inescapable drawbacks that might limit its clinical translation. Compared to stem cells, stem cell-derived exosomes possess numerous advantages, such as non-immunogenicity, non-infusion toxicity, easy access, effortless preservation, and freedom from tumorigenic potential and ethical issues. Exosomes can inherit similar therapeutic effects from their parental cells such as embryonic stem cells and adult stem cells through vertical delivery of their pluripotency or multipotency.

Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma.

Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches exhibit promise in GBM treatment; however, the successful translation of these strategies from preclinical models to clinical settings is hindered by inefficient nanoparticle clearance from vital organs. Addressing this concern, we investigated the therapeutic potential of amrubicin (AMR) encapsulated within poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) in combating temozolomide (TMZ) resistant GBM.

Model Selection and Identification of Osteoporosis Risk Factors in Women to Improve Their Healthcare.

Osteoporosis is characterized by low bone mineral density leading to enhanced bone fragility and a consequent increase in fracture risk. The focus of this case-control study was to identify significant socioeconomic risk factors of osteoporosis in Pakistani women and examine how the risk increases for different levels of risk factors. A case-control study was conducted from November 2018 to August 2019 in two main hospitals in Faisalabad, Pakistan.

Long non-coding RNA RP5-821D11.7 promotes proliferation, migration, and epithelial-mesenchymal transition in glioma and glioma stem-like cells.

Long noncoding RNA (lncRNA) has been recently revealed as a main regulatory molecule, which implicates many cellular functions. Studies showed that lncRNA abnormally expressed and involved in the progression and tumorigenesis of glioma. Present study identified a novel lncRNA associated with glioma, glioma stem-like cells (GSCs), and then revealed their potential functions.

Comparison of physiotherapy with and without intra-articular corticosteroid injection for treatment of frozen shoulder: A comparative study.

Objective: To compare the combination of corticosteroid injection and physiotherapy with physiotherapy alone in patients of frozen shoulder in terms of SPADI score.

Methods: This study included 80 patients of either gender from PMC and affiliated hospitals of Faisalabad with ages between 18-55 years having frozen shoulder of either gender with more than 1 month duration. Patients having frozen shoulder secondary to trauma, cerebrovascular accident and taking steroid injections were excluded.

Collective influence of substrate chemistry with physiological fluid shear stress on human umbilical vein endothelial cells.

In the treatment of cardiovascular diseases, vascular scaffold materials play an extremely important role. The appropriate substrate chemistries and 15 dynes/cm physiological fluid shear stress (FSS) are both required to ensure normal physiological activity of human umbilical vein endothelial cells (HUVECs). The present study reported the collective influence of substrate chemistries and FSS on HUVECs in the sense of its biological functions.

Design and Optimization of PLGA Particles to Deliver Immunomodulatory Drugs for the Prevention of Skin Allograft Rejection.

: Recent advancements in therapeutic strategies have attracted considerable attention to control the acute organs and tissues rejection, which is the main cause of mortality in transplant recipients. The long-term usage of immunosuppressive drugs compromises the body immunity against simple infections and decrease the patients' quality of life. Tolerance of allograft in recipients without harming the rest of host immune system is the basic idea to develop the therapeutic approaches after induction of donor-specific transplant.

An Artificial Antigen-Presenting Cell Delivering 11 Immune Molecules Expands Tumor Antigen-Specific CTLs in and Murine Melanoma Models.

Antigen-presenting cells expand antigen-specific T cells and for tumor immunotherapy, but are time-consuming to generate and, as live cells, raise biosafety concerns. An alternative is found in cell-free artificial antigen-presenting cells (aAPC), but these only present two or three kinds of immune molecules. Here, we describe a multipotent artificial antigen-presenting cell (MaAPC) that delivered 11 kinds of immune moleclues.

A Tolerogenic Artificial APC Durably Ameliorates Experimental Autoimmune Encephalomyelitis by Directly and Selectively Modulating Myelin Peptide-Autoreactive CD4 and CD8 T Cells.

In this study, a tolerogenic artificial APC (TaAPC) was developed to directly and selectively modulate myelin-autoreactive CD4 and CD8 T cells in the myelin oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune encephalomyelitis in C57BL/6J mice. Cell-sized polylactic-coglycolic acid microparticles were generated to cocouple target Ags (MOG/H-2D-Ig dimer, MOG/I-A multimer), regulatory molecules (anti-Fas and PD-L1-Fc), and "self-marker" CD47-Fc and encapsulate inhibitory cytokine (TGF-β1). Four infusions of the TaAPCs markedly and durably inhibited the experimental autoimmune encephalomyelitis progression and reduced the local inflammation in CNS tissue.

Direct modulation of myelin-autoreactive CD4 and CD8 T cells in EAE mice by a tolerogenic nanoparticle co-carrying myelin peptide-loaded major histocompatibility complexes, CD47 and multiple regulatory molecules.

Purpose: Numerous nanomaterials have been reported in the treatment of multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). But most of these nanoscale therapeutics deliver myelin antigens together with toxins or cytokines and underlay the cellular uptake and induction of tolerogenic antigen-presenting cells by which they indirectly induce T cell tolerance. This study focuses on the on-target and direct modulation of myelin-autoreactive T cells and combined use of multiple regulatory molecules by generating a tolerogenic nanoparticle.

On-target and direct modulation of alloreactive T cells by a nanoparticle carrying MHC alloantigen, regulatory molecules and CD47 in a murine model of alloskin transplantation.

Biomimetic nanoparticles have been reported as immune modulators in autoimmune diseases and allograft rejections by numerous researchers. However, most of the therapeutics carrying antigens, toxins or cytokines underlay the mechanism of antigen presentation by cellular uptake of NPs through pinocytosis and phagocytosis. Few researches focus on the direct and antigen-specific modulation on T cells by NPs and combined use of multiple regulatory molecules.

Frequency and reactivity of antigen-specific T cells were concurrently measured through the combination of artificial antigen-presenting cell, MACS and ELISPOT.

Conventional peptide-major histocompatibility complex (pMHC) multimer staining, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay cannot concurrently determine the frequency and reactivity of antigen-specific T cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated cell sorting (MACS), and ELISPOT techniques have been integrated into a micro well by coupling pMHC multimers onto cell-sized magnetic beads to characterize AST cell populations in a 96-well microplate which pre-coated with cytokine-capture antibodies. This method, termed AAPC-microplate, allows the enumeration and local cytokine production of AST cells in a single assay without using flow cytometry or fluorescence intensity scanning, thus will be widely applicable.

Inconsistence between number and function of autoreactive T cells in the course of experimental autoimmune encephalomyelitis.

Background: Mouse experimental autoimmune encephalomyelitis (EAE) is widely used model of multiple sclerosis (MS). The role of autoreactive CD4 and CD8 T cells in the development of mouse EAE has been demonstrated. However, little information is available about the relation between the frequency and reactivity of myelin antigen-reactive CD4 and CD8 T cells in secondary lymphoid organs and their relevance with the inflammation and pathological lesion of CNS during the course of EAE mouse model.

An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8 T Cells.

Selectively depleting the pathogenic T cells is a fundamental strategy for the treatment of allograft rejection and autoimmune disease since it retains the overall immune function of host. The concept of killer artificial antigen-presenting cells (KaAPCs) has been developed by co-coupling peptide-major histocompatibility complex (pMHC) multimer and anti-Fas monoclonal antibody (mAb) onto the polymeric microparticles (MPs) to induce the apoptosis of antigen-specific T cells. But little information is available about its therapeutic potential and mechanism.

Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial polymer antigen-presenting cells to expand antigen-specific T cells and inhibit tumor growth in a mouse model.

Accumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the next step in the development of this technology.

A Combination Strategy for Construction of Peptide-β2m-H-2K Single Chain with Overlap Extension PCR and One-Step Cloning.

The time-consuming and high-cost preparation of soluble peptide-major histocompatibility complexes (pMHC) currently limits their wide uses in monitoring antigen-specific T cells. The single-chain trimer (SCT) of peptide-β2m-MHC class I heavy chain was developed as an alternative strategy, but its gene fusion is hindered in many cases owing to the incompatibility between the multiple restriction enzymes and the restriction endonuclease sites of plasmid vectors. In this study, overlap extension PCR and one-step cloning were adopted to overcome this restriction.

A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo.

The specific eradication of pathogenic T cells for the treatment of allograft rejections and autoimmune disorders without impairment of overall immune function is a fundamental goal. Here, cell-sized poly(lactic-co-glycolic acid) microparticles (PLGA MPs) were prepared as a scaffold to co-display the peptide/major histocompatibility complex (pMHC, target antigen) and anti-Fas monoclonal antibody (apoptosis-inducing molecule) for the generation of biodegradable killer MPs. Ovalbumin (OVA) antigen-targeted killer MPs significantly depleted OVA-specific CD8+ T cells in an antigen-specific manner, both in vitro and in OT-1 mice.