ObjectiveTo comprehensively analyze the recent advancements in the field of mesenchymal stem cells (MSCs) derived exosomes (MSCs-exosomes) in tissue repair. MethodsThe literature about MSCs-exosomes in tissue repair was reviewed and analyzed. ResultsExosomes are biologically active microvesicles released from MSCs which are loaded with functional proteins, RNA, and microRNA. Exosomes can inhibit apoptosis, stimulate proliferation, alter cell phenotype in tissue repair of several diseases through cell-to-cell communication. ConclusionMSCs-exosomes is a novel source for the treatment of tissue repair. Further research of MSCs-exosomes biofunction, paracellular transport, and treatment mechanism will help the transform to clinical application.
Bone malignancies exhibit the characteristics of high incidence, poor prognosis, and strong chemoresistance. Exosomal microRNAs can regulate the proliferation of bone malignant cells, improve chemoresistance, influence cell communication and the microenvironment, and have significant potential in the diagnosis and treatment of bone malignancies. Due to their stability, exosomal microRNAs can serve as non-invasive biomarkers for diagnosis and prognosis. However, their widespread application in clinical settings requires standardized research. This review summarizes the progress of exosomal microRNA research in various bone malignancies including osteosarcoma, chondrosarcoma, Ewing sarcoma, and fibrosarcoma, to provide new theoretical foundations and perspectives for the field.
This research aims to investigate the encapsulation and controlled release effect of the newly developed self-assembling peptide R-LIFE-1 on exosomes. The gelling ability and morphological structure of the chiral self-assembling peptide (CSAP) hydrogel were examined using advanced imaging techniques, including atomic force microscopy, transmission electron microscopy, and cryo-scanning electron microscopy. The biocompatibility of the CSAP hydrogel was assessed through optical microscopy and fluorescent staining. Exosomes were isolated via ultrafiltration, and their quality was evaluated using Western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy. The controlled release effect of the CSAP hydrogel on exosomes was quantitatively analyzed using laser confocal microscopy and a BCA assay kit. The results revealed that the self-assembling peptide R-LIFE-1 exhibited spontaneous assembly in the presence of various ions, leading to the formation of nanofibers. These nanofibers were cross-linked, giving rise to a robust nanofiber network structure, which further underwent cross-linking to generate a laminated membrane structure. The nanofibers possessed a large surface area, allowing them to encapsulate a substantial number of water molecules, thereby forming a hydrogel material with high water content. This hydrogel served as a stable spatial scaffold and loading matrix for the three-dimensional culture of cells, as well as the encapsulation and controlled release of exosomes. Importantly, R-LIFE-1 demonstrated excellent biocompatibility, preserving the growth of cells and the biological activity of exosomes. It rapidly formed a three-dimensional network scaffold, enabling the stable loading of cells and exosomes, while exhibiting favorable biocompatibility and reduced cytotoxicity. In conclusion, the findings of this study support the notion that R-LIFE-1 holds significant promise as an ideal tissue engineering material for tissue repair applications.
ObjectiveTo investigate whether exosomes derived from atorvastatin (ATV)-pretreated human umbilical cord mesenchymal stem cells (ATV-MSC-EXO) alleviate high glucose-induced injury in human retinal vascular endothelial cells (HREC) via the protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway. MethodsThe optimal pretreatment concentration of ATV was determined using the cell counting Kit-8 (CCK-8) assay. Exosomes derived from mesenchymal stem cells (MSC-EXO) and ATV-pretreated MSC (ATV-MSC-EXO) were isolated and extracted, and their morphology and surface markers were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting (WB). The uptake capacity of exosomes by human retinal vascular endothelial cells (HREC) was evaluated using a fluorescence labeling assay. In vitro cultured HREC were divided into the following groups: normal control group (NC group), high glucose group (HG group), high glucose+MSC-EXO group (MSC-EXO group), high glucose+ATV-MSC-EXO group (ATV-MSC-EXO group), high glucose+ATV-MSC-EXO+AKT inhibitor group (ATV-MSC-EXO-MK-2206-2HCL group), and high glucose+ATV-MSC-EXO+eNOS inhibitor group (ATV-MSC-EXO-L-NAME group). Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. The protein expression levels of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated protein (Bax), and Caspase-3 were measured by WB. In addition, the regulatory effects of ATV-MSC-EXO on the AKT/eNOS signaling pathway and its downstream functional molecules were analyzed by detecting the phosphorylation levels of AKT (P-AKT/AKT) and eNOS (P-eNOS/eNOS) via WB, the mRNA expression levels of AKT and eNOS by quantitative real-time polymerase chain reaction, and the concentrations of nitric oxide (NO) and endothelin-1 (ET-1) using commercial NO and ET-1 assay kits. ResultsThe optimal pretreatment concentration of ATV was 1 μmol/L. ATV-MSC-EXO exhibited similar morphology and particle size to MSC-EXO and were efficiently taken up by HREC. Under high glucose conditions, ATV-MSC-EXO significantly enhanced the viability of HREC (F=83.24, P＜0.000 1) and inhibited apoptosis (F=77.39, P＜0.000 1). WB analysis further confirmed that ATV-MSC-EXO upregulated the expression of the anti-apoptotic protein Bcl-2 (F=53.17), while downregulating the pro-apoptotic proteins Bax (F=36.49) and Caspase-3 (F=60.75) (P＜0.001). In addition, ATV-MSC-EXO markedly increased the protein levels of P-AKT/AKT (F=107.60) and P-eNOS/eNOS (F=38.59), as well as the relative mRNA expression of AKT, eNOS (F=203.60, 315.00; P＜0.000 1). Furthermore, ATV-MSC-EXO promoted NO production (F=407.40) and suppressed the relative expression of ET-1 (F=49.76) (P＜0.000 1). ConclusionATV-MSC-EXO enhances the viability and inhibits apoptosis of HREC under high glucose conditions by activating the AKT/eNOS signaling pathway.
Epilepsy is a common neurological disease with complex etiology and various seizure forms. It can affect people of all ages. Although a variety of antiseizure medications are available, one-third of patients still have poor drug treatment. Therefore, better methods for the diagnosis and treatment of epilepsy are particularly important. Exosomes are extracellular vesicles with a diameter of 30 ~ 150 nm that have powerful intercellular information transmission functions and also play an important role in the central nervous system. Exosomes released by nerve cells in the local microenvironment can participate in nerve development and plasticity, regulate neuroinflammation, and reduce neuronal loss. Moreover, some proteins or micro ribonucleic acid (miRNA) in exosomes are highly correlated with epilepsy and are changed in epileptogenesis, so they play an important role in the prevention and early diagnosis of epilepsy. In addition, exosomes have better biocompatibility and lower immunogenicity. Its small size can effectively avoid the phagocytosis of mononuclear macrophages. Moreover, the proteins carried on its surface have a strong homing ability to target tissues or cells and can penetrate the blood-brain barrier to the intracranial, so exosomes have the advantage of natural drug delivery. Therefore, this study reviews the application of exosomes in epilepsy to improve the understanding of exosomes in scientific research and clinical workers.
ObjectiveTo observe the effect of exosomes secreted by retinal pigment epithelial (RPE) cells which damaged by blue light to Nod-like receptor protein (NLRP3).MethodsCultured ARPE-19 cells were divided into 2 groups; one group of RPE cells were exposed to blue light irradiation for 6 hours, the other group was cultured in routine environment. Total exosomes were extracted from the two groups by differential ultracentrifugation in low-temperature, and examined by transmission electron microscope to identify their forms. The exosomes were then incubated with normal ARPE-19 cells. The expression level of CD63, interleukin (IL)-1β, IL-18 and caspase-1 on the exosome surface were measured by Western blotting. The expressions of NLRP3 mRNA in RPE cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR).ResultsBlue light damaged the cellular morphology. Transmission electron microscopy showed that the exosomes were 50-200nm in diameter and like double-concave disks. Blue light damaged cell-derived exosomes had significantly higher expression of IL-1β (t=18.04), IL-18 (t=12.55) and caspase-1 (t=14.70) than the control group (P＜0.001). ARPE-19 cells cultured with blue light damaged cell-derived exosomes also had significantly higher expression of IL-1β (t=18.59), IL-18 (t=23.95) and caspase-1 (t=35.27) than control exosomes (P＜0.001). RT-PCR showed that the relative expression of NLRP3 mRNA of PRE cells in experimental group and control group were 1.000±0.069 and 0.2±0.01, respectively, the difference was significant (t=12.20, P＜0.001).ConclusionThe expression IL-1β, IL-18 and caspase-1 and NLRP3 mRNA were upregulated by exosomes secreted by blue light damaged-RPE cells.
Exosomes are a type of tiny vesicles released by cells, which contain bioactive molecules such as proteins, nucleic acids, and lipids secreted by cells. Exosomes released by different cells play an important role in tumor development and metastasis. These exosomes can regulate the tumor microenvironment, promote the tumor growth and invasion, and participate in the process of distant metastasis by carrying specific proteins and nucleic acids. In addition, some biomarkers in exosomes can serve as potential biomarkers for early diagnosis and prognosis evaluation of osteosarcoma. This article reviews the research progress of exosomes in osteosarcoma, aiming to gain a deeper understanding of their mechanisms of action in this disease and provide a reference for the development of new treatment strategies and prognostic evaluation indicators.
Mesenchymal stem cells (MSCs) are considered as an ideal treatment for multiple diseases including ocular disease. Recent studies have demonstrated that MSCs-derived exosomes have similar functions with MSCs. Exosomes are nanovesicles surrounded by a phospholipid layer that shuttle active cargo between different cells. They are capable of passing the biological barrier and have potentials to be utilized as natural carrier for the ocular drug delivery.
ObjectiveTo observe the effects of exosomes derived from rat mesenchymal stem cells (MSC-exosomes) on the rat experimental autoimmune uveitis (EAU) model.MethodsTwelve Lewis rats were randomly divided into experimental group and control group by random number table, with 6 rats in each group. Rats in the experimental group were established with EAU model, 100 μl of MSC-exosomes (50 μg) were periocular injected on the 9th day after modeling while the control rats were injected with the same volume of phosphate buffer. At different time points after modeling, the retinal structure was observed by hematoxylin and eosin (HE) staining, and the clinical and pathological manifestations were evaluated. T cells from the two groups were analyzed by flow cytometry. Immunohistochemical staining was used to observe the expression of macrophage surface marker CD68. The effect of MSC-exosomes on T cells was measured by lymphocyte proliferation assays. And flow cytometry was used to detect Th1, Th17 and regulatory T cells Variety. Electroretinogram (ERG) was used to evaluate the retinal function. Data were compared between the two groups using the t test.ResultsHE staining showed that the retina structure of the experimental group was more complete than that of the control group on the 15th day after modeling. Immunohistochemical staining showed that the positive expression of CD68 in the experimental group was significantly less than that in the control group. On the 15th day after modeling, the retinal pathological score of the experimental group was lower than that of the control group. On the 9th to 13th day after modeling, compared to the control group, the average clinical scores of the retina in the experimental group were lower, and the difference was statistically significant (t=3.665, 3.21, 3.181, 4.121, 3.227; P＜0.01). The results of T cell proliferation assay showed that exosomes (1.0, 10.0 μg/ml) inhibited the proliferation of T cells under different concentrations of R16 (1, 10, 30 μg/ml), and the difference was statistically significant (F=11.630, 4.188, 6.011; P＜0.05). The results of flow cytometry showed that the number of Th1, Th17 and Treg cell subsets in the experimental group was decreased compared with the control group, and the difference was statistically significant (t=7.374, 4.525, 6.910; P＜0.01). There was no difference in the proportion of cells in the T cells and lymph nodes (t=1.126, 0.493, 0.178; P=0.286, 0.632, 0.862). The results of ERG showed that, compared with the control group, the amplitudes of 0.01, 3.0 cd/m2 a wave and b wave of the experiment group were all increased on the 15th day after modeling, and the differences were statistically significant (t=3.604, 4.178, 4.551, 2.566, P＜0.05).ConclusionsMSC-exosomes can reduce the clinical and pathological manifestations of EAU, protect retinal function, reduce ocular macrophage infiltration, down-regulate the proportion of inflammatory cells in the eye, and inhibit T cell proliferation.
ObjectiveTo review the mechanisms of bioactive substances of mesenchymal stem cells-derived exosomes (MEX) in tissue repair and analyze the therapeutic values of MEX. MethodRecent relevant literature about MEX for tissue repair was extensively reviewed and analyzed. ResultsThe diameter of exosomes ranges from 30 to 100 nm which contain an abundance of bioactive substances, such as mRNA, microRNA, and protein. The majority of the exact bioactive substances in MEX, which are therapeutically beneficial to a wide range of diseases, are still unclear. ConclusionsBioactive substances contained in the MEX have repairing effect in tissue injury, which could provide a new insight for the clinical treatment of tissue damage. However, further studies are required to investigate the individual differences of MEX and the possible risk of accelerating cancer progression of MEX.