Cell-derived Exosomes Research Articles

Harnessing Tumor Cell-Derived Exosomes for Immune Rejection Management in Corneal Transplantation.

Transplantation remains the definitive treatment for end-stage organ failures, but its efficacy is frequently compromised by immune rejection. This study introduces a novel strategy by utilizing tumor-derived exosomes from B16-F10 melanoma cells (B16-Exo), diverging from the conventional use of immune cell-derived exosomes, to alleviate post-transplantation immune rejection. Utilizing murine corneal transplantation as a model, it is demonstrated that B16-Exo significantly reduces immune rejection, evidenced by decreased corneal opacity, neovascularization, and immune dysregulation, while enhancing postoperative survival. Proteomic analyses reveal differential expression of pivotal proteins in B16-Exo, notably the JAK2 protein within the JAK-STAT signaling pathway, which has been mechanistically demonstrated to amplify the activity of myeloid-derived suppressor cells (MDSCs) and inhibit T cell proliferation. These findings demonstrate the significant immunomodulatory effect of B16-Exo in transplant immunology, supporting the continued exploration of tumor-derived exosomes as a platform to uncover novel immunosuppressive mechanisms in transplantation.

Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium-Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats.

Mesenchymal stem cells-derived exosomes (MSCs-EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs-EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4-weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ-diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic-treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H2O2) inflammatory (IL-6, TNF-α, and TGF-β), and apoptotic (P53, BAX, caspase-3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.

Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes.

Extensive tumor microenvironment (TME) and tumor-associated macrophages (TAMs) contribute to the initiation and progression of pancreatic cancer (PC). Cancer cell-derived exosomal miRNAs that stimulate macrophage M2 polarization might play an important role in the process. In the current study, we observed significant upregulation of miR-510 in PC cell lines in comparison to normal HPDE cell line, with PANC-1 exhibiting the highest and MIA PaCa-2 the lowest miR-510 levels. Functional assays demonstrated that miR-510 overexpression enhanced, while its inhibition reduced, PC cell viability, migration, invasion, and EMT. In vivo, miR-510 mimics promoted tumor growth and macrophage M2 polarization, whereas miR-510 inhibition had the opposite effect. Exosomes from PANC-1 and MIA PaCa-2 cells, characterized by nanoparticle tracking analysis and TEM, contained significantly higher miR-510 levels than those from HPDE cells. Macrophages incubated with conditioned media from these PC cells showed increased M2 polarization markers, a process inhibited by the exosome inhibitor GW4869. The delivery of miR-510 via PC cell-derived exosomes facilitated macrophage M2 polarization and regulated the STAT signaling pathway, suggesting that exosomal miR-510 plays a crucial role in the tumor microenvironment of PC by modulating macrophage M2 polarization.

BMSC Derived Exosomes Attenuate Apoptosis of Temporomandibular Joint Disc Chondrocytes in TMJOA via PI3K/AKT Pathway.

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) are crucial means of intercellular communication and can regulate a range of biological processes by reducing inflammation, decreasing apoptosis and promoting tissue repair. We treated temporomandibular joint (TMJ) disc chondrocytes with TNF-α and performed local injection of sodium iodoacetate (MIA) in the TMJ of rats to establish in vitro and in vivo models of TMJ osteoarthritis (TMJOA). BMSC-Exos were isolated and extracted to evaluate their proliferation and trilineage differentiation abilities, and their antiapoptotic and chondroprotective effects were assessed. This study revealed that BMSC-Exos can be endocytosed by TMJ disc chondrocytes in vitro and that BMSC-Exos pretreatment strongly attenuated the inhibitory effect of TNF-α on the proliferative and chondrogenic potential of TMJ disc chondrocytes. The administration of BMSC-Exos significantly suppressed TNF-α-induced apoptosis in TMJ disc chondrocytes by increasing the phosphorylation level of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) pathway-related proteins, whereas the PI3K inhibitor LY294002 neutralized this antiapoptotic effect. Intradiscal injection of BMSC-Exos alleviated the degeneration and inflammation of TMJ discs in a rat model of TMJOA. Our study revealed that BMSC-Exos can attenuate the apoptosis of TMJ disc chondrocytes and destruction of TMJ discs partially by inhibiting the apoptotic pathway and activating the PI3K/AKT pathway, thereby providing a promising treatment strategy for the regeneration of damaged TMJ discs.

Bone marrow mesenchymal stem cell-derived exosomes improve cancer drug delivery in human cell lines and a mouse osteosarcoma model

IntroductionOsteosarcoma is the most common primary bone tumor. Patients require chemotherapy drugs with high-targeting ability and low off-target toxicity to improve their survival. Exosomes are biological vesicles that mediate long-distance communication between cells and naturally target their source sites. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) naturally target bone tumor sites, suggesting their potential as effective anti-tumor therapy vectors. In this study, we evaluated the potential of BMSC-derived exosomes in targeting osteosarcoma and serving as a carrier for doxorubicin (DOX).MethodsWe isolated exosomes from human BMSCs and synthesized hybrid exosomes (HEs) by fusing these exosomes with liposomes. These HEs were loaded with DOX to produce a novel drug, HE/DOX.ResultsWe confirmed the successful synthesis of HE/DOX using fluorescence spectroscopy and estimated its size to be 151.1 ± 10.2 nm. HEs expressed the known exosomal proteins ALIX, CD63, and TSG101. Under acidic conditions similar to those observed in the tumor microenvironment, the drug release from HE/DOX was enhanced. In osteosarcoma cell lines and in a mouse osteosarcoma model, HE/DOX exhibited stronger tumor-inhibitory effects than free DOX.ConclusionsOur study demonstrates that BMSC-derived exosomes could effectively target osteosarcoma. Furthermore, HEs can serve as effective carriers of DOX, enabling the treatment of osteosarcoma. These findings highlight a promising direction for tumor-targeted therapy.

Effect of nHA/CS/PLGA delivering adipose stem cell-derived exosomes and bone marrow stem cells on bone healing-in vitro and in vivo studies.

Adipose stem cell-derived exosomes (ADSC-EXO) have been demonstrated to promote osteogenic differentiation of bone marrow stem cells (BMSCs) and facilitate bone regeneration. The present study aims to investigate the effect of ADSC-EXO-loaded nano-hydroxyapatite/chitosan/poly-lactide-co-glycolide (nHA/CS/PLGA) scaffolds on maxillofacial bone regeneration using tissue engineering. ADSC-EXO was isolated and co-cultured with BMSCs, and the osteogenic differentiation of BMSCs was assessed through the detection of mineralized nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). The nHA/CS/PLGA scaffolds were fabricated and loaded with ADSC-EXO and BMSCs, and these tissue engineering complexes were applied to the maxillofacial bone defect region of rabbits to elucidate their bone regeneration effect. The osteogenic differentiation of BMSCs was markedly enhanced when they were co-cultured with ADSC-EXO. This was evidenced by an increase in the formation of mineralized nodule formation, ALP activity, and mRNA expression of COL1A1 and runt-related transcription factor 2 (RUNX2). In vivo experiments demonstrated that the application of ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds effectively repaired maxillofacial bone defects in rabbits. ADSC-EXO has been demonstrated to promote the osteogenic differentiation of BMSCs. The ADSC-EXO and BMSCs loaded nHA/CS/PLGA scaffolds have been shown to facilitate the regeneration of maxillofacial bone defects. This may serve as a potential therapeutic strategy for large-scale bone defects.

Mesenchymal stem cell-derived exosomes in renal ischemia-reperfusion injury: a new therapeutic strategy.

Renal ischemia-reperfusion injury (RIRI) is a serious kidney condition that causes significant damage due to lack of blood flow. This injury leads to oxidative stress and inflammation, which can cause acute tubular necrosis and kidney failure. Stem cell-derived exosomes, small vesicles released by stem cells, have shown promise in treating RIRI. Mesenchymal stem cells (MSCs) have been used to mitigate RIRI, and their exosomes have been found to play a crucial role in repairing damaged tissues. This review explores the key roles of exosomes from different sources of MSCs in RIRI, the potential of MSC-derived exosomes in treating this disease, and future research directions.

PD-L2 of tumor-derived exosomes mediates the immune escape of cancer cells via the impaired T cell function

The function of PD-1/PD-L1 axis have been intensively studied for immune escape of various cancers. However, the underlying function of PD-L2 remains poorly understood. Here, we demonstrate that PD-L2 is majorly expressed in exosomes with surface localization by clear cell renal cell carcinoma (ccRCC) cells. Tumor cell-derived exosome PD-L2 (TDE-PD-L2) exhibits high expression compared with TDE-PD-L1 in various cancers. In the absence of adaptive immune, TDE-PD-L2 suppresses tumor growth and metastasis. Under immune competence condition, TDE-PD-L2 is hijacked by immune cells in a PD-1-dependent manner to systematically dampen function of T cells via the increased proportion of the regulatory T cells and the decreased proportion of cytotoxic CD8+ T cells in both tumor-infiltrating T cells and spleen. The effects of TDE-PD-L2 on tumor is restored by antibodies targeting PD-L2. Collectively, we demonstrate that PD-1/TDE-PD-L2 axis systematically suppresses T cell functions, representing a potentially therapeutic strategy for ccRCC treatment.

Mesenchymal stem cell-derived exosomes carrying miR-486-5p inhibit glycolysis and cell stemness in colorectal cancer by targeting NEK2

Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC.

Exosomes derived from Umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway.

Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy

BackgroundCisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources.MethodsHuman chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo.ResultsCompared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo.ConclusionsDDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.Graphical abstract

Immune Cell-Derived Exosomes: A Cell-Free Cutting-Edge Tumor Immunotherapy.

Extracellular vesicles (EVs) are cellular communication molecules and are classified into three major subpopulations, such as microvesicles, apoptotic bodies, and exosomes. Among these, exosomes-based cancer research is a cutting-edge investigation approach to cancer understanding. During cancer progression , tumor-derived exosomes can reprogram the cellular system and promote cancer. Circulating exosomes in the body fluids such as blood, plasma, serum, saliva, CSF, sweat, and tears play a key role in identifying diagnostic and prognostic cancer biomarkers. Diverse therapeutic sources of exosomes including stem cells, plants, and immune cells, etc. exhibit significant cancer-healing properties. Although cancer-targeting immunotherapy is an effective strategy, it has limitations such as toxicity, and high costs. In comparison, immune cell-derived exosomes-based immunotherapy is a cell-free approach for cancer treatment and has advantages like less toxicity, biocompatibility, reduced immunogenicity, and efficient, target-specific cancer therapeutic development. This review highlights the therapeutic signature of immune cell-derived exosomes for cancer treatment.

PM2.5 Promotes Macrophage-Mediated Inflammatory Response Through Airway Epithelial Cell-Derived Exosomal miR-155-5p.

Airway epithelial cells (AECs) and alveolar macrophages are involved in airway inflammation. The direct effects of atmospheric fine-particulate-matter (PM2.5) on airway cells, such as AECs and alveolar macrophages, have been widely investigated, but the effect of cell-cell interaction on inflammatory response remains unclear. Exosomes play a crucial role in intercellular communication. However, the cellular interaction of exosomes in PM2.5-induced airway inflammation is unclear. The PM2.5-induced human bronchial epithelial (BEAS-2B) cells and phorbol 12-myristate 13-acetate-induced macrophages (Mφ) were co-cultured and then the expression of IL-6, IL-1β, TNF-α and miRNA-155-5p were detected. Exosomes from PM2.5-exposed BEAS-2B cells were then co-cultured with Mφ to detect the expression of miR-155-5p and inflammatory cytokines, as well as cytokine signaling inhibitor-1 (SOCS1)/NFκB, and to detect the effect of the exosome inhibitor GW4869. After the co-culture of PM2.5-induced BEAS-2B cells and Mφ, the expression of Mφ-derived IL-6, IL-1β, and TNF-α, as well as miRNA-155-5p were upregulated. The expression of miRNA-155-5p was upregulated in BEAS-2B and BEAS-2B cell-derived exosomes after exposure to PM2.5. Furthermore, co-culturing exosomes derived from PM2.5-exposed BEAS-2B cells with Mφ, upregulated miR-155-5p and inflammatory cytokines, decreased cytokine signaling inhibitor-1 (SOCS1) expression, and activated NF-κB. In addition, adding exosome inhibitor GW4869 to PM2.5-interfered BEAS-2B cells co-culture with Mφ downregulated miRNA-155-5p expression, inhibited NF-κB, and reduced the levels of inflammatory factors. PM2.5 promotes Mφ inflammation by upregulating miRNA-155-5P in exosomes obtained from BEAS-2B cells through miR-155-5P/SOCS1/NF-κB pathway. Exosomal miRNAs mediate cellular communication between BEAS-2B cells and Mφ, which may be a new mechanism of PM2.5-stimulated pulmonary inflammatory response.

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

Vericiguat enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction through microRNA-1180-3p/ETS1 pathway

Vericiguat enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction through microRNA-1180-3p/ETS1 pathway

Crosstalk between non-coding RNA and apoptotic signaling in diabetic nephropathy.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in diabetes mellitus. It is also a significant contributor to cardiovascular morbidity and mortality in diabetic patients Thereby, Innovative therapeutic approaches are needed to retard the initiation and advancement of DN. Hyperglycemia can induce apoptosis, a regulated form of cell death, in multiple renal cell types, such as podocytes, mesangial cells, and proximal tubule epithelial cells, ultimately contributing to the pathogenesis of DN. Recent genome-wide investigations have revealed the widespread transcription of the human genome, resulting in the production of numerous regulatory non-protein-coding RNAs (ncRNAs), including microRNAs (miRNAs) and diverse categories of long non-coding RNAs (lncRNAs). They play a critical role in preserving physiological homeostasis, while their dysregulation has been implicated in a broad spectrum of disorders, including DN. Considering the established association between apoptotic processes and the expression of ncRNAs in DN, a thorough understanding of their intricate interplay is essential. Therefore, the current work thoroughly analyzes the intricate interplay among miRNAs, lncRNAs, and circular RNAs in the context of apoptosis within the pathogenesis of DN. Additionally, in the final section, we demonstrated that ncRNA-mediated modulation of apoptosis can be achieved through stem cell-derived exosomes and herbal medicines, presenting potential avenues for the treatment of DN.

NK Cell-Based Cancer Immunotherapies: Current Progress, Challenges and Emerging Opportunities.

Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole-cell therapy, NK cell-derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell-based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research.

Prospective Application of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Disseminated Intravascular Coagulation

Prospective Application of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Disseminated Intravascular Coagulation

Exosomes serve as a crucial mediator of epithelial–fibroblast communication during hair follicle morphogenesis in cashmere goats

The formation of dermal condensates (DCs) through fibroblasts is a pivotal event in hair follicle morphogenesis in cashmere goats, a process that intricately involves epithelial-fibroblast communication. Exosomes (Exos), as essential mediators of intercellular communication, have garnered increasing attention in recent years, yet their precise role in hair follicle morphogenesis remains largely unknown. In this study, we focused on isolating and identifying epithelial cell-derived exosomes (Epi-Exos) from Inner Mongolian cashmere goats. Our experiments demonstrated that Epi-Exos could efficiently enter fibroblasts within 12 h of co-culture. Both direct co-culture of epithelial cells with fibroblasts and co-culture with Epi-Exos alone revealed that Epi-Exos promoted fibroblast migration while inhibiting their proliferation, changes that mirror the cellular biological characteristics observed during DC formation. Furthermore, recognizing the abundance of miRNAs carried by Exos, we conducted small RNA sequencing (small RNA-seq) on Epi-Exos. This analysis identified a panel of 54 highly expressed miRNAs within the Epi-Exos, 34 of which were also found to be abundant in fetal skin tissues of Inner Mongolian cashmere goats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these miRNAs were significantly enriched in cellular processes and signaling pathways related to hair follicle morphogenesis. Notably, our findings offer new perspectives on the role of miRNAs in Epi-Exos regulating DC formation and hair follicle morphogenesis in cashmere goats, with significant implications for understanding hair follicle development mechanisms and potential clinical or production benefits, including improved cashmere quality and yield through targeted exosome-mediated signaling manipulation.

Dendritic Cell-Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy

Dendritic Cell-Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy