Host and Pathogen-Directed Therapies against Microbial Infections Using Exosome- and Antimicrobial Peptide-derived Stem Cells with a Special look at Pulmonary Infections and Sepsis

Moghaddam, Mehrdad Moosazadeh; Fazel, Parvindokht; Fallah, Arezoo; Sedighian, Hamid; Kachuei, Reza; Behzadi, Elham; Fooladi, Abbas Ali Imani

doi:10.1007/s12015-023-10594-2

Cited by 5 publications

(6 citation statements)

References 251 publications

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“…In recent years, stem cell-derived exosomes therapy have received much attention as factors regulating the immune system. The therapeutic effects of exosomes on the immune system is based on the HDT strategy ( Moosazadeh Moghaddam et al., 2023 ).…”

Section: Tlrs Immunity and Infectionmentioning

confidence: 99%

“…Exosomes are the smallest extracellular vesicle (EV) structures that can be produced by a wide variety of cells. EVs are generally categorized into three main groups based on size: large-sized apoptotic bodies (1000–5000 nm) are generated during apoptosis; medium-sized micro vesicles (100–1000 nm) secreted from the cell plasma membrane, small-sized vesicles or exosomes (<30–150 nm) produced via the endocytic pathway ( Pegtel and Gould, 2019 ; Moosazadeh Moghaddam et al., 2023 ). Exosomes vesicles are enclosed in a phospholipid bilayer membrane which originated from the endocytic route and the plasma membrane inward budding results in the formation of these nanovesicles ( Figure 5 ) ( Kalluri and LeBleu, 2020 ; Dudzik et al., 2021 ).…”

Section: Exosomes-tlrs Intraction and Infection Controlmentioning

confidence: 99%

“…Exosomes have significant roles in physiology and immunity and have known to play dual roles in both immune system activation and immune suppression ( Moosazadeh Moghaddam et al., 2023 ). However, there are evidences that exosomes generally downregulate immune processes in the absence of stress and pathology ( Fleshner and Crane, 2017 ).…”

Section: Exosomes-tlrs Intraction and Infection Controlmentioning

confidence: 99%

“…In recent years, stem cell-derived exosomes have received much attention as factors regulating the immune system. The significant advantage of exosomes is that they have many characteristics of their parent cells, and on the other hand, exosomes do not have many of the limitations that exist in the use of cells ( Moosazadeh Moghaddam et al., 2023 ; Essola et al., 2024 ). Studies have proven that cell receptors such as TLRs can be transferred from cell to cell through exosomes to cause functional changes in the recipient cells.…”

Section: Introductionmentioning

confidence: 99%

“…The HDT approach underpins the therapeutic effects of exosomes on the immune system. The stem cell-derived exosomes function in HDT through immune regulation and modulation, tissue regeneration stimulation, and decreased toxicity to the host ( Zhang et al., 2019 ; Moosazadeh Moghaddam et al., 2023 ). Accordingly, studies have demonstrated that one of the most significant exosomal cargoes that can control inflammatory responses is microRNA (miRNA).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Moghaddam,

Behzadi,

Sedighian

et al. 2024

Front. Cell. Infect. Microbiol.

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Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host’s defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

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Section: Tlrs Immunity and Infectionmentioning

confidence: 99%

Section: Exosomes-tlrs Intraction and Infection Controlmentioning

confidence: 99%

Section: Exosomes-tlrs Intraction and Infection Controlmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Moghaddam,

Behzadi,

Sedighian

et al. 2024

Front. Cell. Infect. Microbiol.

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A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

Alshahrani,

Jasim,

Altalbawy

et al. 2024

Cell Biochemistry & Function

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Mesenchymal stem cell‐derived exosomes (MSC‐Exos) are emerging as remarkable agents in the field of immunomodulation with vast potential for diagnosing and treating various diseases, including cancer and autoimmune disorders. These tiny vesicles are laden with a diverse cargo encompassing proteins, nucleic acids, lipids, and bioactive molecules, offering a wealth of biomarkers and therapeutic options. MSC‐Exos exhibit their immunomodulatory prowess by skillfully regulating pattern‐recognition receptors (PRRs). They conduct a symphony of immunological responses, modulating B‐cell activities, polarizing macrophages toward anti‐inflammatory phenotypes, and fine‐tuning T‐cell activity. These interactions have profound implications for precision medicine, cancer immunotherapy, autoimmune disease management, biomarker discovery, and regulatory approvals. MSC‐Exos promises to usher in a new era of tailored therapies, personalized diagnostics, and more effective treatments for various medical conditions. As research advances, their transformative potential in healthcare becomes increasingly evident.

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Hydrogels loaded with MSC‐derived small extracellular vesicles: A novel cell‐free tissue engineering system for diabetic wound management

Zhong,

Meng,

et al. 2024

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With the aging and obesity era, the increasing incidence of diabetes and diabetic complications, especially the non‐healing wounds, imposes a serious economic burden on both patients and society. The complex microenvironments, including hyperglycemia, bacterial infection, ischemia, and nerve damage, lead to the prolonged inflammation and proliferation phase of diabetic wounds. Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs), which contain a rich variety of therapeutic molecules, have been chased for decades because of their potential roles in cellular communication, tissue regeneration, and drug delivery. As powerful tools for the controlled‐sustained release of sEVs, biocompatible hydrogels have been applied in a wide range of biomedical applications. Herein, we first summarize the pathological features of diabetic wounds, such as angiopathy, neuropathy, and immune cell dysfunction. Then, we discuss the biological properties, therapeutic performance, and stability of pure MSC‐sEVs. After that, we discuss the components, application patterns, and responsiveness of hydrogels. Next, we discuss the loading avenues of MSC‐sEVs into hydrogel, the release behaviors of sEVs from hydrogels, and the influence of the crosslinking method on the hydrogel‐sEV composites. Finally, we provide an overview of the current applications of hydrogels loaded with MSC‐sEVs as a novel cell‐free tissue engineering system in managing diabetic wounds and propose the critical unsolved issues. This review is expected to provide meaningful guidance for developing a novel cell‐free tissue engineering system for diabetic wound management.

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Host and Pathogen-Directed Therapies against Microbial Infections Using Exosome- and Antimicrobial Peptide-derived Stem Cells with a Special look at Pulmonary Infections and Sepsis

Cited by 5 publications

References 251 publications

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes

A comprehensive insight into the immunomodulatory role of MSCs‐derived exosomes (MSC‐Exos) through modulating pattern‐recognition receptors (PRRs)

Hydrogels loaded with MSC‐derived small extracellular vesicles: A novel cell‐free tissue engineering system for diabetic wound management

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