Confined-Coordination Induced Intergrowth of Metal-Organic Frameworks into Precise Molecular Sieving Membranes.

Metal-organic framework (MOF) membranes with rich functionality and tunable pore system are promising for precise molecular separation; however, it remains a challenge to develop defect-free high-connectivity MOF membrane with high water stability owing to uncontrollable nucleation and growth rate during fabrication process. Herein, we report on a confined-coordination induced intergrowth strategy to fabricate lattice-defect-free Zr-MOF membrane towards precise molecular separation. The confined-coordination space properties (size and shape) and environment (water or DMF) were regulated to slow down the coordination reaction rate via controlling the counter-diffusion of MOF precursors (metal cluster and ligand), thereby inter-growing MOF crystals into integrated membrane. The resulting Zr-MOF membrane with angstrom-sized lattice apertures exhibits excellent separation performance both for gas separation and water desalination process. It was achieved H2 permeance of ~1200 GPU and H2/CO2 selectivity of ~67; water permeance of ~8 L ⋅ m-2 ⋅ h-1 ⋅ bar-1 and MgCl2 rejection of ~95 %, which are one to two orders of magnitude higher than those of state-of-the-art membranes. The molecular transport mechanism related to size-sieving effect and transition energy barrier differential of molecules and ions was revealed by density functional theory calculations. Our work provides a facile approach and fundamental insights towards developing precise molecular sieving membranes.

EphA2-specific microvesicles derived from tumor cells facilitate the targeted delivery of chemotherapeutic drugs for osteosarcoma therapy.

Despite advances in surgery and chemotherapy, the survival of patients with osteosarcoma (OS) has not been fundamentally improved over the last two decades. Microvesicles (MVs) have a high cargo-loading capacity and are emerging as a promising drug delivery nanoplatform. The aim of this study was to develop MVs as specifically designed vehicles to enable OS-specific targeting and efficient treatment of OS. Herein, we designed and constructed a nanoplatform (YSA-SPION-MV/MTX) consisting of methotrexate (MTX)-loaded MVs coated with surface-carboxyl Fe3O4 superparamagnetic nanoparticles (SPIONs) conjugated with ephrin alpha 2 (EphA2)-targeted peptides (YSAYPDSVPMMS, YSA). YSA-SPION-MV/MTX showed an effective targeting effect on OS cells, which was depended on the binding of the YSA peptide to EphA2. In the orthotopic OS mouse model, YSA-SPION-MV/MTX effectively delivered drugs to tumor sites with specific targeting, resulting in superior anti-tumor activity compared to MTX or MV/MTX. And YSA-SPION-MV/MTX also reduced the side effects of high-dose MTX. Taken together, this strategy opens up a new avenue for OS therapy. And we expect this MV-based therapy to serve as a promising platform for the next generation of precision cancer nanomedicines.

Mesenchymal stem cell-derived exosomes as a promising cell-free therapy for knee osteoarthritis.

Osteoarthritis (OA), as a degenerative disease, leads to high socioeconomic burdens and disability rates. The knee joint is typically the most affected and is characterized by progressive destruction of articular cartilage, subchondral bone remodeling, osteophyte formation and synovial inflammation. The current management of OA mainly focuses on symptomatic relief and does not help to slow down the advancement of disease. Recently, mesenchymal stem cells (MSCs) and their exosomes have garnered significant attention in regenerative therapy and tissue engineering areas. Preclinical studies have demonstrated that MSC-derived exosomes (MSC-Exos), as bioactive factor carriers, have promising results in cell-free therapy of OA. This study reviewed the application of various MSC-Exos for the OA treatment, along with exploring the potential underlying mechanisms. Moreover, current strategies and future perspectives for the utilization of engineered MSC-Exos, alongside their associated challenges, were also discussed.

Effect of polyaniline dispersibility in chitin sponge matrix controlled by hydrophilicity on microplastics adsorption.

Microplastics have become an emerging threat to global ecosystems, and their efficient removal faces with serious challenges. Herein, this study introduced different hydrophilic polyaniline (PANIs) into chitin matrix to fabricate Chitin-PANIs sponge (ChPANIs) and investigated the relationship between PANIs dispersibility in chitin sponge matrix controlled by its hydrophilicity and adsorption effects on MPs. With the increase of PANIs' hydrophilicity (WCA from 153.9° to 32.8°), the removal efficiency of sponges to MPs increased from 84.0 % to 91.7 %. More hydrophilic PANIs can provide more contact surfaces and adsorption sites, which enhanced the electrostatic interactions to MPs and obtained excellent adsorption properties. The adsorption of MPs on ChPANIs accorded with the pseudo-first-order adsorption, suggesting that physical adsorption plays a dominant role. The adsorption process also conformed to Freundlich model, which displayed the MPs adsorption on ChPANI-PA could be multi-layer. The adsorption strength of ChPANIs was 0.7552, suggesting that it was a strong adsorbent. The ChPANIs also exhibited good mechanical properties and reusability, which its MPs removal efficiency just decreased from 91.7 % to 86.9 % during the five cycles. These findings expand the understanding of the adsorption mechanism analysis of MPs on sponge materials, and exist guiding significance for the design of adsorbed materials.

Insights into FcγR involvement in pain-like behavior induced by an RA-derived anti-modified protein autoantibody.

Joint pain is one of the most debilitating symptoms of rheumatoid arthritis (RA) and patients frequently rate improvements in pain management as their priority. RA is hallmarked by the presence of anti-modified protein autoantibodies (AMPA) against post-translationally modified citrullinated, carbamylated and acetylated proteins. It has been suggested that autoantibody-mediated processes represent distinct mechanisms contributing to pain in RA. In this study, we investigated the pronociceptive properties of monoclonal AMPA 1325:01B09 (B09 mAb) derived from the plasma cell of an RA patient. We found that B09 mAb induces pain-like behavior in mice that is not associated with any visual, histological or transcriptional signs of inflammation in the joints, and not alleviated by non-steroidal anti-inflammatory drugs (NSAIDs). Instead, we found that B09 mAb is retained in dorsal root ganglia (DRG) and alters the expression of several satellite glia cell (SGC), neuron and macrophage-related factors in DRGs. Using mice that lack activating FcγRs, we uncovered that FcγRs are critical for the development of B09-induced pain-like behavior, and partially drive the transcriptional changes in the DRGs. Finally, we observed that B09 mAb binds SGC in vitro and in combination with external stimuli like ATP enhances transcriptional changes and protein release of pronociceptive factors from SGCs. We propose that certain RA antibodies bind epitopes in the DRG, here on SGCs, form immune complexes and activate resident macrophages via FcγR cross-linking. Our work supports the growing notion that autoantibodies can alter nociceptor signaling via mechanisms that are at large independent of local inflammatory processes in the joint.

Zr-MOF membranes with ultra-fast water-selective permeation towards intensification of esterification reaction.

Well-intergrown polycrystalline UiO-66 membranes were successfully synthesized on a polymeric substrate under mild synthesis conditions of a lower temperature and short synthesis time. The resulted UiO-66 membranes with fast water selective transport channels exhibited unprecedentedly high solvent dehydration performance with a permeation flux of ∼6100 g m-2 h-1 and a separation factor of ∼7500, showing great potential for intensification of esterification reaction.

Mulberroside A alleviates osteoarthritis via restoring impaired autophagy and suppressing MAPK/NF-κB/PI3K-AKT-mTOR signaling pathways.

Osteoarthritis (OA) is a trauma-/age-related degenerative disease characterized by chronic inflammation as one of its pathogenic mechanisms. Mulberroside A (MA), a natural bioactive withanolide, demonstrates anti-inflammatory properties in various diseases; however, little is known about the effect of MA on OA. We aim to examine the role of MA on OA and to identify the potential mechanisms through which it protects articular cartilage. In vitro, MA improved inflammatory response, anabolism, and catabolism in IL-1ß-induced OA chondrocytes. The chondroprotective effects of MA were attributed to suppressing the MAPK, NF-κB, and PI3K-AKT-mTOR signaling pathways, as well as promoting the autophagy process. In vivo, intra-articular injection of MA reduced the cartilage destruction and reversed the change of anabolic and catabolic-related proteins in destabilized medial meniscus (DMM)-induced OA models. Thus, the study indicates that MA exhibits a chondroprotective effect and might be a promising agent for OA treatment.

Decreased Peli1 expression attenuates osteoarthritis by protecting chondrocytes and inhibiting M1-polarization of macrophages.

AIMS: Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA. METHODS: After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1ß was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry. RESULTS: In chondrocytes, knockdown of Peli1 produced anti-inflammatory and anti-apoptotic effects by targeting the TLR and NF-κB signalling pathways. We found that in macrophages, knockdown of Peli1 can inhibit M1-type polarization of macrophages. In addition, the corresponding conditioned culture medium of macrophages applied to chondrocytes can also produce an anti-apoptotic effect. During in vivo experiments, the results have also shown that knockdown Peli1 reduces cartilage destruction and synovial inflammation. CONCLUSION: Knockdown of Peli1 has a therapeutic effect on OA, which therefore makes it a potential therapeutic target for OA.Cite this article: Bone Joint Res 2023;12(2):121-132.

Extracellular vesicles as an emerging drug delivery system for cancer treatment: Current strategies and recent advances.

Cancer is one of the primary causes of death worldwide, and its morbidity and mortality rates are increasing rapidly. However, standard treatment modalities (surgery, radiotherapy, chemotherapy, and immunotherapy) often fail to achieve a satisfactory therapeutic effect. Extracellular vesicles (EVs) are natural nano-sized lipid bilayer vesicles secreted from cells. Owing to their advantages of low toxicity, high biocompatibility, low immunogenicity, and inherent targeting, EVs can be exploited as drug delivery vectors for cancer treatment. In this review, we summarize the research progress of EV-based drug delivery systems in cancer treatment by focusing on four aspects: sources, cargo types, cargo loading methods and modification strategies. Finally, current challenges and future perspectives are discussed.

Glycogen Synthase Kinase 3ß inhibits BMSCs Chondrogenesis in Inflammation via the Cross-Reaction between NF-κB and ß-Catenin in the Nucleus.

Inflammation can influence the pluripotency and self-renewal of mesenchymal stem cells (MSCs), thereby altering their cartilage regeneration ability. Sprague-Dawley (SD) rat bone marrow mesenchymal stem cells (BMSCs) were isolated and found to be defective in differentiation potential in the interleukin-1ß- (IL-1ß-) induced inflammatory microenvironment. Glycogen synthase kinase-3ß (GSK-3ß) is an evolutionarily conserved serine/threonine kinase that plays a role in numerous cellular processes. The role of GSK-3ß in inflammation may be related to the nuclear factor-κB (NF-κB) signaling pathway and the Wnt/ß-catenin signaling pathway, whose mechanism remains unclear. In this study, we found that GSK-3ß can inhibit chondrogenesis of IL-1ß-impaired BMSCs by disrupting metabolic balance and promoting cell apoptosis. By using the inhibitors LiCl and SN50, we demonstrated that GSK-3ß regulates the chondrogenesis via the NF-κB and Wnt/ß-catenin signaling pathways and possibly mediates the cross-reaction between NF-κB and ß-catenin in the nucleus. Given the molecular mechanisms of GSK-3ß in chondrogenic differentiation in inflammation, GSK-3ß is a crucial target for the treatment of inflammation-induced cartilage disease.

Machine Learning for the Prediction of Synchronous Organ-Specific Metastasis in Patients With Lung Cancer.

Background: This study aimed to develop an artificial neural network (ANN) model for predicting synchronous organ-specific metastasis in lung cancer (LC) patients. Methods: A total of 62,151 patients who diagnosed as LC without data missing between 2010 and 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) program. The ANN model was trained and tested on an 75/25 split of the dataset. The receiver operating characteristic (ROC) curves, area under the curve (AUC) and sensitivity were used to evaluate and compare the ANN model with the random forest model. Results: For distant metastasis in the whole cohort, the ANN model had metrics AUC = 0.759, accuracy = 0.669, sensitivity = 0.906, and specificity = 0.613, which was better than the random forest model. For organ-specific metastasis in the cohort with distant metastasis, the sensitivity in bone metastasis, brain metastasis and liver metastasis were 0.913, 0.906 and 0.925, respectively. The most important variable was separate tumor nodules with 100% importance. The second important variable was visceral pleural invasion for distant metastasis, while histology for organ-specific metastasis. Conclusions: Our study developed a "two-step" ANN model for predicting synchronous organ-specific metastasis in LC patients. This ANN model may provide clinicians with more personalized clinical decisions, contribute to rationalize metastasis screening, and reduce the burden on patients and the health care system.

Effective removal of humic acid by mesoporous Zr-MOF adjusted through SDBS.

Humic acid (HA) in makeup water is one of the important safety issues of high-parameter power plants. Herein, the Zr-based metal-organic frameworks (NH2-UiO-66) was applied to remove humic acid in water. The mesoporous of NH2-UiO-66 was controlled by surfactants sodium dodecyl benzene sulfonate (SDBS) to increase the adsorption of HA. The adsorption of HA at 25°C and pH 7 increased fast at the first 0.5 h and then gradually reached equilibrium after 10 h. The maximum adsorption capacity was 108.93 mg g-1, which removal efficiency was high as 95.0%. The morphology and adsorption properties of NH2-UiO-66 were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), surface charge, Fourier transform infrared (FT-IR), N2 adsorption-desorption, and adsorption test. The adsorption process of HA accorded with the pseudo-second-order kinetics, while the adsorption isotherm conformed to be the Langmuir model and the adsorption was proved to be monolayer adsorption. Adsorption was the spontaneous and endothermic process (ΔG°<0, ΔH°>0). The accessible surface area provided by mesopores on the 5 different Zr-MOFs was the reason for the enhanced HA adsorption capacity. These results provided useful information for effective HA removing and enhanced our understanding of the adsorption mechanism of HA on NH2-UiO-66.

Cyclic mechanical strain with high-tensile triggers autophagy in growth plate chondrocytes.

BACKGROUND: Mechanical loading has been widely considered to be essential for growth plate to maintain metabolism and development. Cyclic mechanical strain has been demonstrated to induce autophagy, whereas the relationship between cyclic tensile strain (CTS) and autophagy in growth plate chondrocytes (GPCs) is not clear. The objective of this study was to investigate whether CTS can regulate autophagy in GPCs in vitro and explore the potential mechanisms of this regulation. METHODS: The 2-week-old Sprague-Dawley rat GPCs were subjected to CTS of varying magnitude and duration at a frequency of 2.0 Hz. The mRNA levels of autophagy-related genes were measured by RT-qPCR. The autophagy in GPCs was verified by transmission electron microscopy (TME), immunofluorescence and Western blotting. The fluorescence-activated cell sorting (FACS) was employed to detect the percentage of apoptotic and necrotic cells. RESULTS: In GPCs, CTS significantly increased the mRNA and protein levels of autophagy-related genes, such as LC3, ULK1, ATG5 and BECN1 in a magnitude- and time-dependent manner. There was no significant difference in the proportion of apoptotic and necrotic cells between control group and CTS group. The autophagy inhibitors, 3-methyladenine (3MA) and chloroquine (CQ) reversed the CTS-induced autophagy via promoting the formation of autophagosomes. Cytochalasin D (cytoD), an inhibitor of G-actin polymerization into F-actin, could effectively block the CTS-induced autophagy in GPCs. CONCLUSION: Cyclic mechanical strain with high-tensile triggers autophagy in GPCs, which can be suppressed by 3MA and CQ, and cytoskeletal F-actin microfilaments organization plays a key role in chondrocytes' response to mechanical loading.

Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVß3 and Exerts Chondroprotective Effect.

Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1ß-induced chondrocyte inflammation response. Moreover, PA reduced IL-1ß-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1ß-induced chondrocytes could be reversed when integrin αVß3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVß3. Thus, PA or integrin αVß3 might be a promising agent or molecular target for the treatment of OA.

Chitosan nanoparticles fabricated through host-guest interaction for enhancing the immunostimulatory effect of CpG oligodeoxynucleotide.

CpG oligodeoxynucleotides (CpG ODNs) which can induce innate immune responses and promote adaptive immune responses, are powerful tools in defeating diseases. Here, a novel chitosan nanoparticle (CS-NPs) based on host-guest interaction has been designed for encapsulation and delivery of CpG ODNs for the first time. The CS-NPs exhibited high encapsulation efficiency (98.3%) of CpG ODNs and remained stable in storage under room temperature for at least 7 days. CS-NPs can also prevent CpG ODN diffusion at pH 7. The results of confocal laser scanning microscope images and flow cytometry show that CS-NPs can also be efficiently delivered into living cells. Furthermore, CpG@CS-NPs can increase the immunostimulatory activity of CpG ODNs. Raw 264.7 cells treated with CpG@CS-NPs demonstrated upregulation of both TNF-α and IL-6 cytokines by 13% and 40%, respectively. The newly developed CpG@CS-NPs were thus identified as an efficient system to deliver CpG-ODNs to treat various diseases.

Biodegradable and re-usable sponge materials made from chitin for efficient removal of microplastics.

Microplastics have attracted widespread attention due to their detrimental effects on organisms, and their efficient removal poses great challenges, especially those smaller than 3 µm that are more harmful for aquatic biota. Herein, the chitin based sponges with interconnected pores, excellent elasticity and mechanical durability were fabricated and composed with graphene oxide (GO) and oxygen-doped carbon nitride (O-C3N4). The chitin based sponges could effectively remove different functionalized microplastics (~1 µm) at pH 6-8, including carboxylate-modified polystyrene (PS-COOH), amine-modified polystyrene (PS-NH2), and polystyrene (PS). Notably, the removal efficiency of three microplastics by the chitin based sponges reached up to 71.6-92.1% at an environmentally relevant concentration of 1 mg L-1 in water system. The potential driving forces of the adsorption were electrostatic interactions, hydrogen bond interactions, and π-π interactions. In addition, the chitin based sponges are reusable and after re-used for 3 cycles due to their excellent compressibility. The algae toxicity test demonstrated good biocompatibility of the chitin based sponges and they are also biodegradable in a natural soil. This study provides a green and promising method for fabricating environmentally friendly adsorbents for small-size microplastics removal, and expands the insights into the mechanisms of microplastic adsorption onto the sponge materials.

Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids facilitates the repair of cardiotoxin-induced skeletal muscle injury in fat-1 mice.

In this study, we investigated the beneficial effects of high endogenous levels of n-3 polyunsaturated fatty acids (PUFAs) on skeletal muscle repair and regeneration using a mouse cardiotoxin (CTX, 20 µM/200 µL) -induced gastrocnemius muscle injury model. Transgenic fat-1 mice expressing the Caenorhabditis elegans fat-1 gene, encoding n-3 fatty acid desaturase, showed higher n-3 PUFA levels and lower n-6/n-3 PUFA ratios in gastrocnemius muscle tissues. Hematoxylin and eosin and Masson's trichrome staining of gastrocnemius sections revealed increased muscle fiber size and reduced fibrosis in fat-1 mice on days 7 and 14 after CTX injections. Gastrocnemius muscle tissues from fat-1 mice showed reduced inflammatory responses and increased muscle fiber regeneration reflecting enhanced activation of satellite cells on day 3 after cardiotoxin injections. Gastrocnemius muscle tissues from cardiotoxin-treated fat-1 mice showed reduced levels of pro-apoptotic proteins (Caspase 3 and Bax) and increased levels of anti-apoptotic proteins (Bcl-2 and Survivin). Moreover, eicosapentaenoic acid (EPA) reduced the incidence of apoptosis among cardiotoxin-treated C2C12 mouse myoblasts. These findings demonstrate that higher endogenous n-3 PUFA levels in fat-1 mice enhances skeletal muscle repair and regeneration following cardiotoxin-induced injury.

Incidence and survival outcomes of secondary liver cancer: a Surveillance Epidemiology and End Results database analysis.

BACKGROUND: The global incidence and mortality rates of liver cancer, which is the second leading cause of cancer-related deaths worldwide, are increasing. However, information on its epidemiology and clinical prognosis is limited. This study aimed to characterize the epidemiology and prognostic factors of secondary liver cancer to aid in the pretreatment evaluation of the disease. METHODS: Patients diagnosed with secondary liver cancer between 2010 and 2014 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included. Kaplan-Meier analysis and Multivariate Cox regression analysis were performed to screen for significant factors associated with secondary liver cancer. RESULTS: A total of 85,738 secondary liver cancer patients were identified; in this population, the first primary site was the lung (25.9%), followed by the colorectum, pancreas, stomach, breast, and cecum. Patients with primary tumors of the colorectum, cecum and breast had longer median survival time. Advanced age, male gender, black race, poor differentiation or lack of differentiation, regional lymph node metastases, and presence of distant metastasis were associated with poor prognosis. CONCLUSIONS: In this study, novel findings on the role of the primary site and synchronous distant metastasis to specific organs in patients with secondary liver cancer were described. These findings have significant implications in clinical diagnosis and treatment, and provide a better understanding of secondary liver cancer in the general population.

Insight into Morphology Change of Chitin Microspheres using Tertiary Butyl Alcohol/H2 O Binary System Freeze-Drying Method.

The morphology of materials usually plays a significant role in their applications; the mechanical properties of the materials and characteristics such as specific surface area, surface energy, adsorbability, and wettability are dependent on the morphology. This study is focused on studying the effects of different tertiary butyl alcohol (TBA) aqueous solutions on the freeze-dried morphologies of chitin microspheres (CMs). By constructing a TBA/H2 O phase diagram, the underlying mechanisms of morphology change are explored. It is found that by freeze drying the CMs with 20 and 100 wt% TBA, a fine nanofiber weaved pore structure can be obtained. Away from these two ratios, the nanofibers are oppressed by the large crystals formed during the precool process or bind together due to the existence of water in the secondary drying stage, poor morphology and pore characteristics appearing. Moreover, the 20 wt% TBA freeze-drying route is conducive to split the CMs and other polysaccharide (PS) microspheres. The split method is also helpful for exploring the internal structure of the microspheres. Therefore, this study makes it possible to simplify the morphology control of CMs, which helps in the characterization of porous PS-based microspheres.

Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, the relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference. METHODS: In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1014 proteins were detected using a label-free method. RESULTS: Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow MSC-derived exosomes showed superior regeneration ability, and adipose tissue MSC-derived exosomes played a significant role in immune regulation, whereas umbilical cord MSC-derived exosomes were more prominent in tissue damage repair. CONCLUSIONS: This study systematically and comprehensively analyzes the human MSC-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies.