Exosome Therapy Research Articles

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These cargo molecules are encapsulated in a lipid bilayer and internalized by target cells through receptor-ligand interactions or lipid membrane fusion. With the advancement of exosome research, exosome therapy for osteoporosis is fast becoming a research hotspot for researchers. This review aims to discuss the role of exosomes in the pathogenesis of osteoporosis. In addition, emerging diagnostic and therapeutic properties of exosomes are described to highlight the potential role of exosomes in osteoporosis.

Potential Therapeutic Strategies for Skeletal Muscle Atrophy.

The maintenance of muscle homeostasis is vital for life and health. Skeletal muscle atrophy not only seriously reduces people's quality of life and increases morbidity and mortality, but also causes a huge socioeconomic burden. To date, no effective treatment has been developed for skeletal muscle atrophy owing to an incomplete understanding of its molecular mechanisms. Exercise therapy is the most effective treatment for skeletal muscle atrophy. Unfortunately, it is not suitable for all patients, such as fractured patients and bedridden patients with nerve damage. Therefore, understanding the molecular mechanism of skeletal muscle atrophy is crucial for developing new therapies for skeletal muscle atrophy. In this review, PubMed was systematically screened for articles that appeared in the past 5 years about potential therapeutic strategies for skeletal muscle atrophy. Herein, we summarize the roles of inflammation, oxidative stress, ubiquitin-proteasome system, autophagic-lysosomal pathway, caspases, and calpains in skeletal muscle atrophy and systematically expound the potential drug targets and therapeutic progress against skeletal muscle atrophy. This review focuses on current treatments and strategies for skeletal muscle atrophy, including drug treatment (active substances of traditional Chinese medicine, chemical drugs, antioxidants, enzyme and enzyme inhibitors, hormone drugs, etc.), gene therapy, stem cell and exosome therapy (muscle-derived stem cells, non-myogenic stem cells, and exosomes), cytokine therapy, physical therapy (electroacupuncture, electrical stimulation, optogenetic technology, heat therapy, and low-level laser therapy), nutrition support (protein, essential amino acids, creatine, β-hydroxy-β-methylbutyrate, and vitamin D), and other therapies (biomaterial adjuvant therapy, intestinal microbial regulation, and oxygen supplementation). Considering many treatments have been developed for skeletal muscle atrophy, we propose a combination of proper treatments for individual needs, which may yield better treatment outcomes.

GMP-Compliant Mesenchymal Stem Cell-Derived Exosomes for Cell-Free Therapy in Cancer.

Cancer is categorized as one of the life-threatening disease in the world, which has recently been associated with a significant increase in the incidence and prevalence rate. Hence, the discovery of effective approaches for prevention, early diagnosis, and effective treatment for cancer has been prioritized by oncology researchers. In recent decades, mesenchymal stem cells show great potential to advance the field of regenerative medicine and oncology research due to representing prominent characteristics. Recently, studies indicate that mesenchymal stem cells can play an important role by secreting extracellular vesicles like exosomes in modulating the biological functions of target cells through paracrine regulation. Indeed, the exosomes derived from mesenchymal stem cells can represent the same therapeutic potential as parent cells with fewer side effects. Therefore, it can be demonstrated that exosomes can be a suitable drug delivery candidate in regenerative medicine and targeted therapy. It is also noteworthy that as the use of exosome therapy becomes more common in clinical studies, the importance of improving basic criteria such as safety, efficiency, and quality of stem cell products will also be highlighted. Based on this concept, the good manufacturing practice principles were put forward to examine the standard of cell products from different qualitative and quantitative aspects to progress the cell therapy. In other words, the principles of good manufacturing practice should be observed not only in the extraction and isolation of stem cells but also in the extraction of products related to stem cells such as exosomes in the field of treatment.

Comparison and Investigation of Exosomes from Human Amniotic Fluid Stem Cells and Human Breast Milk in Alleviating Neonatal Necrotizing Enterocolitis

In view of the devastating impact of neonatal necrotizing enterocolitis (NEC) on newborns, the research on its intervention is particularly important. Although exosomes from human amniotic fluid stem cells (AFSC) and human breast milk (HBM) can protect against NEC, their mechanisms remain unclear. Here, we intend to compare the intervention effects of two types of exosomes on NEC mouse model and reveal their respective regulatory mechanisms. In general, both AFSC-derived exosomes (AFSC-exos) and HBM-derived exosomes (HBM- exos) can alleviate NEC- associated intestinal injury, significantly reduce NEC score, and reduce systemic and ileal inflammation and NEC related brain injury during experimental NEC. However, the mode and mechanism of action of the two sources of exosomes were not identical. In vivo, the number of ileal crypts was more significantly restored after HBM-exos intervention than AFSC-exos, and in vitro, HBM-exos preferentially inhibited the inflammatory response of intestinal epithelial cells (IECs), whereas AFSC-exos preferentially regulated the migration of IECs. Mechanistically, GO and KEGG analyses revealed the different therapeutic mechanisms of AFSC-exos and HBM-exos in NEC. Taken together, our results illustrate that AFSC-exos and HBM-exos reduce the severity of experimental NEC and intestinal damage through different mechanisms, supporting the potential of cell-free or breast milk free exosome therapy for NEC.Graphical

Abstract 15228: Manganese-Enhanced MRI (MEMRI) Determines the Mechanistic Efficacy of Exosome Therapy in a Porcine Myocardial Infarction Model

Introduction: Transplantation of exosomes from mesenchymal stem cells (MSCs) and induced pluripotent stem cell derived cardiomyocytes (iCMs) improves heart function after myocardial infarction (MI). However, imaging methods have not been established to assess the mechanism of these treatments. Contrast imaging with gadolinium delayed-enhancement MRI (DEMRI) allows non-specific quantification of myocardial fibrosis. In contrast, MEMRI demonstrates active uptake of manganese into intracellular space by the viable cardiomyocytes via L-type calcium channel. MEMRI delineates the level of cellular metabolism and identifies the recovery of the injured but viable cardiomyocytes in the peri-infarct region (PIR). Hypothesis: MEMRI reflects the mechanistic efficacy of cell therapy. Methods: Yorkshire swine were subject to percutaneous proximal left anterior descending artery occlusion for 1 hour. Ten 500ul injections containing 5 x 10 11 exosomes isolated from MSCs and iCMs were delivered transendocardially to the PIR. Four weeks after injury, left ventricular ejection fraction (LVEF), and myocardial scar/viability were measured. DEMRI and MEMRI delineated the PIR to quantify the effects of exosomes. Results: The LVEF of PBS (control), MSC-exosome, and iCM-exosome groups was 18.66% ± 4.23, 27.46% ± 6.16, and 29.5% ± 3.96*, respectively (*p<0.05). The % contrast enhancement by DEMRI over total LV volume were 29.38% ± 4.86, 28.76% ± 5.02, and 29.58% ± 5.55, respectively. Meanwhile, the % contrast nulling (CN, non-viable) by MEMRI were 20.51% ± 3.86, 9.53% ± 1.99, and 7.31% ± 2.62*, respectively (*p<0.01). mRNA seq of the porcine myocardium and subsequent gene ontology and KEGG analyses demonstrated significant differential gene expression of iCM-exosome group related to calcium regulation (adenylate cyclase 7, 3.30-fold change) and sarcoplasmic reticulum calcium ion transport (chemokine receptor 5, 3.15-fold change). Conclusions: The % CN reduction of MEMRI reflects improved cardiomyocyte metabolism and calcium handing by exosome therapy. The underlying mechanism and functional improvement are identified by MEMRI.

Abstract 11725: Exosomes Secreted from TSG6-Rich Adipose-Derived Stem Cells Induce Neovascularization in Ischemic Limb

Introduction: Therapeutic angiogenesis is attractive for tackling cardiovascular disease. Exosomes, which contain growth factors and micro RNAs, might be useful to develop cell-free therapeutic angiogenesis. Previously we have reported that CD271+ADRCs have excellent angiogenic activity. In this study, we investigated the in vivo angiogenic effects and mechanisms of CD271+ ADSC-derived exosomes (CD271+ Exo) using a mouse model of limb ischemia. Methods: We analyzed single-cell RNA-sequencing data of human stromal vascular fraction (SVF) cells. After normalization and clustering, CD271+ and CD271- cells were analyzed in DESeq2. Next, we established CD271+/- ADSCs from human SVF using FACS. After 48 hours of serum deprivation, conditioned media was collected. Exosomes were purified by magnetic isolation using phosphatidylserine/Tim4 interaction and confirmed by ELISA of exosomal markers. We labeled exosomes by PKH26 membrane dye and injected them into a mice model of limb ischemia. After 2 weeks, lectin perfused limb was harvested and analyzed by immunohistochemistry (Fig.A). Results: In single-cell transcriptome of human SVF, TSG6 was predominantly expressed in Lineage-CD34+ stromal cells. Furthermore, TSG6 was significantly upregulated in CD271+ SVF cells compared to CD271- SVF cells and other cluster cells (Fig.B). Consistently, TSG6 mRNA expression was upregulated in CD271+ ADSCs (Fig.C). We confirmed exosomal marker expression (CD63, CD9, and CD81) of isolated Exo (Fig.D). In exosome therapy, CD271+ Exo promotes neovascularization compared to CD271- Exo or PBS. Notably, there were more cells containing PKH labeling in the CD271+ Exo-treated group (Fig.E). Conclusions: This study reveals a novel mechanism by which CD271+ Exo promotes angiogenesis via TSG6. CD271+ Exo would be useful for cell-free therapeutic angiogenesis.

Abstract 11511: Stem Cell-Derived Exosome Nebulization Therapy (SCENT) Promotes Cardiac Repair After Myocardial Infarction by Inhibiting CD36

Introduction: Stem cell-derived exosomes are promising therapeutics for cardiac repair after injury. Since they have short half-life in vivo, efficient exosome therapies need repeated dosing. Here, we develop a noninvasive and repeatable method for exosome delivery via a nebulizer after myocardial infarction (MI), named Stem Cell-Derived Exosome Nebulization Therapy (SCENT). Methods: Lung spheroid cell-derived-exosomes were isolated from secretome by ultrafiltration and characterized by a Zetasizer. We labelled them with a NIR-680 dye, before delivering them to C57BL/6 mice with MI model via a nebulizer for 7 consecutive days. IVIS live imaging and fluorescent microscopy was used to detect the biodistribution of exosomes in vivo and ex vivo. Echocardiographies were performed to monitor the cardiac function after SCENT in MI mouse and histological analysis helped investigating the myocardial repair, in comparison with the controls. Single-cell sequencing of the whole heart was performed to explore the mechanism of action after SCENT. Results: Homing of exosomes to the ischemic heart after SCENT was detected by immunofluorescence microscopy (Fig. 1a). SCENT led to significantly improved left ventricular function to our mouse MI model at 2 weeks (EF: 66.97 ± 2.49%), compared to that of MI control (EF: 36.13 ± 3.57%) (Fig. 1b) , along with reduced infarct size (Fig. 1c). Single-cell sequencing revealed a significant downregulation of CD36 in cardiac endothelial cells, which suppressed the transport and uptake of fatty acids in myocardium, leading to a compensatory increase in glucose utilization and cardiomyocyte proliferation (Fig. 1d,e) . Conclusions: Exosomes delivered by SCENT were recruited to the ischemic heart, which promoted function recovery and cardiac repair in a mouse MI model. This therapeutic effect was attributed to the inhibition of endothelial CD36. SCENT gives a promising solution for the repeatable and noninvasive treatment for heart repair.

Stem Cell Exosome Therapy Recovers Mitochondrial Respiration in Hypoxic Cardiomyocytes

Stem Cell Exosome Therapy Recovers Mitochondrial Respiration in Hypoxic Cardiomyocytes

HUMSC vs. hUMSC-Exosome: Which One Is Better for Epilepsy?

Epilepsy is a disorder characterized by abnormal brain cell activity that results in seizures. It causes progressive damage to neurons. Epilepsy treatment currently focuses mostly on symptoms, which also have risks of unwanted side effects. There is currently no effective treatment to prevent epileptogenesis and the resulting neural damage. Human Umbilical Cord Mesenchymal Stem Cell (hUMSC) and exosome therapy are examples of cellular therapies that may be used to treat degenerative diseases, such as epilepsy, or cell damage. However, there is still little research on the use of hUMSCs or hUMSC–exosomes for treating epilepsy. Hence, the purpose of this paper is to compare the potential and risk of hUMSCs and hUMSC–exosomes as therapies for epilepsy. This article provides a brief summary of hUMSCs and hUMSC–exosomes in multiple aspects, such as the isolation and purification method, the mechanism of action, immunological compatibility, tumorigenicity, the risk of transmitting disease, stability upon storage, the potential of new composition with other substances, and also ethical and political issues. We conclude that hUMSCs and hUMSC–exosomes have therapeutic potential for epilepsy, with hUMSC–exosomes being safer due to their reduced immunogenicity.

Exosomes and Biomaterials: In Search of a New Therapeutic Strategy for Multiple Sclerosis.

Current efforts to find novel treatments that counteract multiple sclerosis (MS) have pointed toward immunomodulation and remyelination. Currently, cell therapy has shown promising potential to achieve this purpose. However, disadvantages such as poor survival, differentiation, and integration into the target tissue have limited its application. A series of recent studies have focused on the cell secretome, showing it to provide the most benefits of cell therapy. Exosomes are a key component of the cell secretome, participating in the transfer of bioactive molecules. These nano-sized vesicles offer many therapeutical advantages, such as the capacity to cross the blood-brain barrier, an enrichable cargo, and a customizable membrane. Moreover, integrating of biomaterials into exosome therapy could lead to new tissue-specific therapeutic strategies. In this work, the use of exosomes and their integration with biomaterials is presented as a novel strategy in the treatment of MS.

A Triple Therapeutic Strategy with Antiexosomal Iron Efflux for Enhanced Ferroptosis Therapy and Immunotherapy.

Ferroptosis is a form of regulated cell death which can not only kill tumor cells but also enhance immunogenicity of tumor cells, and it is evidenced to be involved in a variety of tumor treatments, especially in cancer immunotherapy. Tumor cell-derived exosomes are reported to influence the progression and metastasis process of tumors. In the process of ferroptosis, exosomes are also demonstrated as mediators to export iron under high intracellular iron concentration and resist ferroptosis. Under this regard, the combined application of ferroptosis inducer and the inhibitor of iron-containing exosomes may enhance the ferroptosis. Herein, biocompatible hybrid nanoparticles composed of the iron oxide nanoparticles, polymers with oxaliplatin attached, and siProminin2 are constructed. The siProminin2 mediated exosomal inhibition can restore the intracellular iron concentration, which can also inhibit the secretion of tumor cell-derived exosomes. The combination of immunotherapy with oxaliplatin, ferroptosis-based cancer therapy and inhibition of tumor cell-derived exosomes can enhance the immune activation effects. The nanoparticles represent an excellent triple therapeutic strategy for enhancing ferroptosis-based cancer therapy and immunotherapy.

Regenerative mesenchymal stem cell‐derived extracellular vesicles: A potential alternative to cell‐based therapy in viral infection and disease damage control

Extracellular vesicles (EVs) released by regenerative cells such as mesenchymal stem cells are effective facilitators of healing, therapy, and repair. Conversely, EVs released from infected and/or diseased cells could be useful as markers in the detection and diagnosis of disease conditions such as cancer at their earliest most detectable, and treatable stage. A very important type of EVs, termed exosomes offer a hypothetical new paradigm in disease detection, diagnosis, and treatment. A broad range of exosome-based biomedical and therapeutic applications are now being evaluated in recent clinical trials. Exosomes are found in virtually all bodily fluids and cells and are capable of crossing tight junctions and toughly regulated boundaries such as the blood-brain barrier. Exosomes' expedition ends when they are taken up by bystander cells which corroborates the fact that they are conduits for cells releasing them. Exosomes released by diseased cells have been associated with cell-to-cell progression of diseases like viral disease, neurodegeneration, and certain cancers. Due to high discrimination in most disease conditions, exosome uptake is usually cell-specific. Lots of research evidence have revealed that infusion of exosomes derived from regenerative cells such as stem cells could impede the development of certain infections and age-related diseases by activating self-repair machinery through RNA, DNA, protein, and lipid transfer between cells in patients. They have also been demonstrated in the restoration of the circulating population of exosomes in tissues and the fluid of recipients. The first human clinical trials of exosome therapies are now underway, establishing the future of regenerative exosome in regenerative medicine. This article is categorized under: Cancer > Stem Cells and Development Immune System Diseases > Stem Cells and Development Immune System Diseases > Molecular and Cellular Physiology.

35326 Exosome therapy for scalp hair growth—A review of the in vivo and in vitro evidence

Background: Exosome therapy is an evolving field that is being investigated for use in treating hair loss. As no human clinical studies exist, we sought to review the in vivo and in vitro available preclinical studies.

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair.

Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.

LB1015 Exosome therapy in hair regeneration: A literature review of the evidence, challenges, and future opportunities

Alopecia is a common chief complaint and is challenging to treat. Exosomes, extracellular vesicles formed by sequential invagination of membranes between intracellular components, are involved in cell communication, homeostasis, and differentiation, and play a key role in hair morphogenesis and regeneration with potential for alopecia treatment use. To summarize the current body of knowledge surrounding exosomes and identify areas for research, a literature review was conducted using keywords including “exosome,” “alopecia,” and “hair loss” on PubMed, EMBASE, and Google Scholar databases to assess exosome use, postulated underlying mechanisms, and clinical applications.

Ginsenoside Rh2 Inhibits NLRP3 Inflammasome Activation and Improves Exosomes to Alleviate Hypoxia-Induced Myocardial Injury.

The inflammatory microenvironment after acute myocardial infarction (MI) is a key limiting factor in the clinical application of stem cell transplantation and paracrine exosome therapy. Qishen Yiqi Pills contain a saponin ingredient called Ginsenoside Rh2 (Rh2) which exhibits a certain therapeutic effect on MI. However, the mechanism by which Rh2 alleviates the inflammatory microenvironment and improves the therapeutic efficiency of exosomes remains enigmatic. Here, we found that Rh2 attenuated the adverse effect of oxygen-glucose deprivation (OGD)-induced cellular injury, an in vitro pathological model of MI. Confocal microscopy revealed that DiI-labeled BMSCs-derived exosomes exhibited an increased homing ability of cardiomyocytes, which, in turn, inhibited the nuclear translocation of NF-κB p65 and NLRP3 inflammasome activation, thereby alleviating the inflammatory microenvironment and further facilitating the homing of exosomes to cardiomyocytes by forming a feed-forward enhancement loop. Additionally, we found that Rh2 could regulate the HMGB1/NF-κB signaling pathway to improve the OGD environment of cardiomyocytes, increasing the efficiency of the feed-forward loop. In conclusion, we found that Rh2 can improve the inflammatory microenvironment by enhancing the protection of exosomes against myocardial injury, providing new insights into the indirect modification of exosomes by Rh2 in MI treatment.

Exosome therapy in hair regeneration: A literature review of the evidence, challenges, and future opportunities.

Alopecia is a common chief complaintand is challenging to treat. As such, regenerative treatments to promote hair growth are an emergingarea of research. Exosomes, which are extracellular vesicles involved in cell communication, homeostasis, differentiation, and organogenesis, have been shown to play a central role in hair morphogenesis and regeneration with potential for use as alopecia treatment. This review summarizes and assesses the body of literature surrounding exosomes as regenerative therapeutics for alopecia and identifies areas for improvement in future research. A review was conducted using a comprehensive list of keywords including "exosome," "alopecia," and "hair loss" on PubMed, EMBASE, and Google Scholar databases published from inception to February 2022. Reference lists of identified articles were included. 47studies were included. Clinical trial databases were searched using the term "exosome"; however, no trials relevant to hair growth were identified. Our updated and comprehensive review details the history of exosome use in medicine, postulated underlying mechanisms in treating hair loss, and current clinical studies. Preclinical studies demonstrate clear benefits of exosome therapeutics in regenerative medicine and for hair loss treatment. Clinical trials demonstrate safety of exosome use in medicine, but data showing efficacy and safety of exosome therapy for alopecia are lacking. We identified several gaps in knowledge required for effective clinical translation including safety, exosome source, and optimal treatment delivery mechanism and dosage. Exosomes are on the horizon as an exciting therapeutic for the treatment of alopecia. Further studies and clinical trials are required.

Significance of Placental Mesenchymal Stem Cell in Placenta Development and Implications for Preeclampsia.

The well-developed placentation is fundamental for the reproductive pregnancy while the defective placental development is the pathogenetic basis of preeclampsia (PE), a dangerous complication of pregnancy comprising the leading causes of maternal and perinatal morbidity and mortality. Placenta-derived mesenchymal stem cells (PMSCs) are a group of multipotent stem cells that own a potent capacity of differentiating into constitutive cells of vessel walls. Additionally, with the paracrine secretion of various factors, PMSCs inextricably link and interact with other component cells in the placenta, collectively improving the placental vasculature, uterine spiral artery remolding, and uteroplacental interface immunoregulation. Recent studies have further indicated that preeclamptic PMSCs, closely implicated in the abnormal crosstalk between other ambient cells, disturb the homeostasis and development in the placenta. Nevertheless, PMSCs transplantation or PMSCs exosome therapies tend to improve the placental vascular network and trophoblastic functions in the PE model, suggesting PMSCs may be a novel and putative therapeutic strategy for PE. Herein, we provide an overview of the multifaceted contributions of PMSCs in early placental development. Thereinto, the intensive interactions between PMSCs and other component cells in the placenta were particularly highlighted and further extended to the implications in the pathogenesis and therapeutic strategies of PE.

Stem Cell-Derived Exosome Therapy for Dental Diseases: From Bench to Bed in Dentistry

Stem cells are undifferentiated cells that have significant potential to regenerate missing tissues and living structures. Exosomes are a specific subgroup of extracellular vesicles that are recognized as important mediators of intercellular communication in the process of regeneration. They contribute to various pathways of physiological and pathological processes. Given the ability of exosomes to carry molecular cargos and transfer bioactive components, exosome-based disease diagnosis and therapeutics have been extensively studied over the past few decades. The present review highlights the emerging applications of exosomes as therapeutic agents in craniofacial and dental regenerative processes. In addition, the current challenges and future perspectives of exosomes in dental clinical applications are discussed. Keywords: dentistry, stem cells, exosome, regeneration, periodontal.

A new horizon of precision medicine: combination of the microbiome and extracellular vesicles.

Over several decades, the disease pattern of intractable disease has changed from acute infection to chronic disease accompanied by immune and metabolic dysfunction. In addition, scientific evidence has shown that humans are holobionts; of the DNA in humans, 1% is derived from the human genome, and 99% is derived from microbial genomes (the microbiome). Extracellular vesicles (EVs) are lipid bilayer-delimited nanoparticles and key messengers in cell-to-cell communication. Many publications indicate that microbial EVs are both positively and negatively involved in the pathogenesis of various intractable diseases, including inflammatory diseases, metabolic disorders, and cancers. Microbial EVs in feces, blood, and urine show significant differences in their profiles between patients with a particular disease and healthy subjects, demonstrating the potential of microbial EVs as biomarkers for disease diagnosis, especially for assessing disease risk. Furthermore, microbial EV therapy offers a variety of advantages over live biotherapeutics and human cell EV (or exosome) therapy for the treatment of intractable diseases. In summary, microbial EVs are a new tool in medicine, and microbial EV technology might provide us with innovative diagnostic and therapeutic solutions in precision medicine.