Inflammatory Bowel Disease (IBD) is a chronic autoimmune disorder that severely affects the gastrointestinal tract and is difficult to cure. This study explored the mechanism by which human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Ex) alleviate IBD through O-GlcNAc glycosylation modification and the expression of related proteins. The study analyzed the effects of HucMSC-Ex on the inhibition of pro-inflammatory factors and promotion of intestinal epithelial cells regeneration in vitro and in vivo, with a focus on the role of the O-GlcNAc glycosylation of the RACK1 protein. The findings indicated that HucMSC-Ex reverses epithelial-mesenchymal transition (EMT) by upregulating O-GlcNAc glycosylation levels and effectively alleviates IBD symptoms and inflammatory responses in mouse intestinal epithelial cells. By modulating O-GlcNAc glycosylation, HucMSC-Ex exhibits significant therapeutic potential in immune regulation and gut microbiota remodeling, offering new perspectives for IBD treatment.

Small extracellular vesicles (sEVs) are membrane-bound vesicles with a size of less than 200 nm, released by cells. Due to their relatively small molecular weight and ability to participate in intercellular communication, sEVs can serve not only as carriers of biomarkers for disease diagnosis but also as effective drug delivery agents. Furthermore, these vesicles are involved in regulating the onset and progression of various diseases, reflecting the physiological and functional states of cells. This paper introduces the classification of extracellular vesicles, with a focus on the extraction and identification of sEVs and their significant role in repair, diagnosis, and intercellular communication. Additionally, the paper addresses the engineering modification of sEVs to provide a reference for enhanced understanding and application.

Non-healing wounds pose significant challenges and require effective therapeutic interventions. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic agents in tissue regeneration. However, the functional differences between different subpopulations of EVs in wound healing remain understudied. This study aimed to evaluate the effects of two distinct subpopulations of clonal mesenchymal stromal cells (cMSC)-derived EVs (cMSC-EVs), namely 20 K and 110K-cMSC-EVs, primarily on in vitro wound healing process, providing fast and cost-effective alternatives to animal models.

In vitro assays were conducted to compare the effects of 20 K and 110K-cMSC-EVs, isolated through high-speed centrifugation and differential ultracentrifugation, respectively. For evaluation the main mechanisms of wound healing, including cell proliferation, cell migration, angiogenesis, and contraction. Human dermal fibroblasts (HDF) were considered as the main cells for analysis of these procedures. Moreover, gene expression analysis was performed to assess the impact of these EV subpopulations on the related process of wound healing on HDF.

The results demonstrated that both 20 K and 110K-cMSC-EVs exhibited beneficial effects on cell proliferation, cell migration, angiogenesis, and gel contraction. RT-qPCR revealed that both EV types downregulated interleukin 6 (IL6), induced proliferation by upregulating proliferating cell nuclear antigen (PCNA), and regulated remodeling by upregulating matrix metallopeptidase 1 (MMP1) and downregulating collagen type 1 (COL1).

This study highlights the effects of both 20 K and 110K-cMSC-EVs on the potency of HDFs in wound healing-related process. As the notable finding, 20K-cMSC-EVs offer a more feasible and cost-effective subpopulation for isolation and follow the GMP standard, recommended to utilize this fraction for therapeutic application.

Exosomal non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, have emerged as crucial modulators in cellular signaling, influencing wound healing processes. Stem cell-derived exosomes, which serve as vehicles for these ncRNAs, show remarkable therapeutic potential due to their ability to modulate wound healing stages, from initial inflammation to collagen formation. These ncRNAs act as molecular signals, regulating gene expression and protein synthesis necessary for cellular responses in healing. Wound healing is a complex, staged process involving inflammation, hemostasis, fibroblast proliferation, angiogenesis, and tissue remodeling. Stem cell-derived exosomal ncRNAs enhance these stages by reducing excessive inflammation, promoting anti-inflammatory responses, guiding fibroblast and keratinocyte maturation, enhancing vascularization, and ensuring organized collagen deposition. Their molecular cargo, particularly ncRNAs, specifically targets pathways to aid chronic wound repair and support scarless regeneration. This review delves into the unique composition and signaling roles of Stem cell-derived exosomes and ncRNAs, highlighting their impact across wound healing stages and their potential as innovative therapeutics. Understanding the interaction between exosomal ncRNAs and cellular signaling pathways opens new avenues in regenerative medicine, positioning Stem cell-derived exosomes and their ncRNAs as promising molecular-level interventions in wound healing.

The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.

This study aimed to explore whether excessive HIF2α can amplify the impact of human Umbilical Cord Mesenchymal Stem Cell-derived Extracellular Vesicles (hUC-MSC- EVs) on endothelial cells.

In this study, we created HIF2α-overexpressing hUC-MSC-EVs and compared their pro-angiogenic effects with control EVs on Human Umbilical Vein Endothelial Cells (HUVECs). MTT assay and Edu staining were used to detect the viability and proliferation ability of HUVECs, and Transwell and Tube Formation Assays were used to detect cell migration and tube formation ability. qPCR assay was used to detect the expression of cellular angiogenic markers. Subsequently, miRNAs that might be regulated by HIF2α were predicted by bioinformatics analysis, and qPCR was used to detect the relative expression of miRNAs in HUVECs treated with hUC-MSC- EV, which over-expresses HIF2α. Subsequently, miR-146a inhibitors were used to investigate the role of miR-146a in mediating the pro-angiogenic effect of HIF2α on HUVECs by detecting cell viability, proliferation, migration, tube-forming ability, and expression of angiogenic markers. Finally, AKT/ERK phosphorylation and Spred1 expression were detected using Western blotting.

Our findings have indicated that overexpression of HIF2α significantly enhances the ability of hUC-MSC-EVs to stimulate proliferation, migration, and tube formation in HUVECs, as demonstrated by MTT/Edu staining, Transwell assay, and tube formation assay results, respectively. Mechanistically, excessive HIF2α has been found to induce the expression of miR-146a in HUVECs and the overexpression of a miR-146a inhibitor to negate the influence of excessive HIF2α on hUC-MSC-EV-induced activity in HUVECs.

The overexpression of HIF2α is an effective strategy for enhancing the pro-angiogenic function of hUC-MSC-EVs.

Stem cell transplantation has proven effective in treating acute and chronic wounds, but its limitations, such as low cellular viability and the need for specialized transportation, highlight the necessity for alternative approaches. This review explores the potential of engineered exosomes, containing identified miRNAs/peptides, as a more stable and efficient cell-free therapy for regenerative medicine, particularly in wound healing. The discussion emphasizes the benefits of exosomes, including their stability, reduced damage, and consistent biological activity, paving the way for innovative applications like lyophilized exosomes, mist spray delivery, and exosome-based scaffolds. The exploration of cell-free therapy in this review holds promising implications for advancing wound-healing strategies.

Peripheral nerve injury (PNI) can cause nerve demyelination, neuronal apoptosis, axonal atrophy, inflammatory infiltration, glial scar formation, and other pathologies that can lead to sensory and motor dysfunction and seriously affect the psychosomatic health of patients. There is currently no effective treatment method, so exploring a promising treatment method is of great significance. Several studies have revealed the therapeutic roles of Schwann cells (SCs) and their exosomes in nerve injury repair. Exosomes are extracellular nanovesicles secreted by cells that act as key molecules in intercellular communication. Progress has been made in understanding the role of exosomes derived from SCs (SC-EXOs) in peripheral nerve regeneration, including the promotion of axonal regeneration and myelin formation, anti-inflammation, vascular regeneration, neuroprotection, and neuroregulation. Therefore, in this paper, we summarize the functional characteristics of SC-EXOs and discuss their potential therapeutic effects on PNI repair as well as some existing problems and future challenges.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, with its incidence rising due to improved survival rates of these infants. BPD results from a combination of prenatal and postnatal factors, such as mechanical ventilation, oxygen toxicity, and infections, all of which significantly impact the prognosis and growth of affected infants. Current treatment options for BPD are largely supportive and do not address the underlying pathology. Exosomes are cell-derived bilayer-enclosed membrane structures enclosing proteins, lipids, RNAs, growth factors, cytokines and metabolites. They have become recognized as crucial regulators of intercellular communication in various physiological and pathological processes. Previous studies have revealed the therapeutic potential of human umbilical cord mesenchymal stem cells-derived exosomes (HUCMSCs-Exos) in promoting tissue repair and regeneration. Therefore, HUCMSCs-Exos maybe a promising and effective therapeutic modality for BPD. In this review, we firstly provide a comprehensive overview of BPD, including its etiology and the mechanisms of lung injury. Then we detail the isolation, characterization, and contents of HUCMSCs-Exos, and discuss their potential mechanisms of HUCMSCs-Exos in BPD treatment. Additionally, we summarize current clinical trials and discuss the challenges in translating these findings from bench to bedside. This review aims to lay the groundwork for future clinical applications of HUCMSCs-Exos in treating BPD.

Stem cells-derived extracellular vesicles (SC-EVs) have emerged as promising therapeutic agents for wound repair, recapitulating the biological effects of parent cells while mitigating immunogenic and tumorigenic risks. These EVs orchestrate wound healing processes, notably through modulating angiogenesis-a critical event in tissue revascularization and regeneration. This study provides a comprehensive overview of the multifaceted mechanisms underpinning the pro-angiogenic capacity of EVs from various stem cell sources within the wound microenvironment. By elucidating the molecular intricacies governing their angiogenic prowess, we aim to unravel the mechanistic repertoire underlying their remarkable potential to accelerate wound healing. Additionally, methods to enhance the angiogenic effects of SC-EVs, current limitations, and future perspectives are highlighted, emphasizing the significant potential of this rapidly advancing field in revolutionizing wound healing strategies.

Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring-called fibrosis-that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies.

Mesenchymal stem cells (MSCs) originating from the umbilical cord (UC) or Wharton's jelly (WJ) have attracted substantial interest due to their potential to augment therapeutic approaches for a wide range of disorders. These cells demonstrate a wide range of capabilities in the process of differentiating into a multitude of cell types. Additionally, they possess a significant capacity for proliferation and are conveniently accessible. Furthermore, they possess a status of being immune-privileged, exhibit minimal tumorigenic characteristics, and raise minimal ethical concerns. Consequently, they are well-suited candidates for tissue regeneration and the treatment of diseases. Additionally, UC-derived MSCs offer a substantial yield compared to other sources. The therapeutic effects of these MSCs are closely associated with the release of nanosized extracellular vesicles (EVs), including exosomes and microvesicles (MVs), containing lipids, microRNAs, and proteins that facilitate intercellular communication. Due to their reduced tumorigenic and immunogenic characteristics, in addition to their convenient manipulability, EVs have arisen as a viable alternative for the management of disorders. The favorable characteristics of UC-MSCs or WJ-MSCs and their EVs have generated significant attention in clinical investigations encompassing diverse pathologies. Therefore, we present a review encompassing current preclinical and clinical investigations, examining the implications of UC-MSCs in diverse diseases, including those affecting bone, cartilage, skin, liver, kidney, neural, lung, cardiovascular, muscle, and retinal tissues, as well as conditions like cancer, diabetes, sepsis, and others.

The treatment of diabetic wounds possessed significant challenges in clinical practice, which was accompanied with continuous infection, inflammation, and limited angiogenesis. Current wound dressings used for diabetic wound healing struggle to address these issues simultaneously. Therefore, Ga3+ was added to the chitosan/silk solution to confer potent antibacterial properties. Subsequently, umbilical cord mesenchymal stem cell exosomes (UCSC-Exo) were integrated into the gallium/chitosan/silk solution to enhance its angiogenesis-inducing activity. The mixture was lyophilized to prepare gallium/chitosan/silk/exosome sponge scaffolds (Ga/CSSF-Exo sponge scaffolds). The experiments of In vitro and in vivo demonstrated that Ga/CSSF-Exo sponge scaffolds exhibited sustained release of Ga3+ and bioactive exosomes, which effectively exerted continuous antibacterial effects and promoted angiogenesis. In diabetic rat wound models, Ga/CSSF-Exo sponge scaffolds facilitated angiogenesis, suppressed bacterial growth and inflammation, as well as promoted collagen deposition and re-epithelialization of wounds. Collectively, our findings suggested that Ga/CSSF-Exo held excellent potential for diabetic wound healing.

Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis.

Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions.

Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression.

UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

Diabetic wounds (DWs) are open sores that can occur anywhere on a diabetic patient's body. They are often complicated by infections, hypoxia, oxidative stress, hyperglycemia, and reduced growth factors and nucleic acids. The healing process involves four phases: homeostasis, inflammation, proliferation, and remodeling, regulated by various cellular and molecular events. Numerous genes and signaling pathways such as VEGF, TGF-β, NF-κB, PPAR-γ, MMPs, IGF, FGF, PDGF, EGF, NOX, TLR, JAK-STAT, PI3K-Akt, MAPK, ERK, JNK, p38, Wnt/β-catenin, Hedgehog, Notch, Hippo, FAK, Integrin, and Src pathways are involved in these events. These pathways and genes are often dysregulated in DWs leading to impaired healing. The present review sheds light on the pathogenesis, healing process, signaling pathways, and genes involved in DW. Further, various therapeutic strategies that target these pathways and genes via nanotechnology are also discussed. Additionally, clinical trials on DW related to gene therapy are also covered in the present review.

Stem cell-derived extracellular vesicles (SCEVs) have emerged as a potential therapy for hemorrhagic stroke. However, their effects are not fully understood. The aim of this study was to comprehensively evaluate the effects of SCEVs therapy in rodent models of hemorrhagic stroke, including subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).

We conducted a comprehensive search of PubMed, EMBASE, and Web of Science until May 2023 to identify studies investigating the effects of SCEVs therapy in rodent models of ICH. The functional outcomes were assessed using neurobehavioral scores. Standardized mean differences (SMDs) and confidence intervals (CIs) were calculated using a random-effects model. Three authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were performed using Revman 5.3 and Stata 17.0.

Twelve studies published between 2018 and 2023 met the inclusion criteria. Our results showed that SCEVs therapy improved neurobehavioral scores in the rodent SAH model (SMD = -3.49, 95% CI: -4.23 to -2.75; p < 0.001). Additionally, SCEVs therapy improved the chronic neurobehavioral scores of the rodent ICH model (SMD = 2.38, 95% CI: 0.36-4.40; p=0.02) but did not have a significant impact on neurobehavioral scores in the acute and subacute phases. Significant heterogeneity was observed among the studies, and further stratification and sensitivity analyses failed to identify the source of heterogeneity.

Our findings suggest that SCEVs therapy may improve neurofunctional behavior after hemorrhagic stroke and provide important insights into the design of preclinical trials.

Exosomes are extracellular vesicles of diverse compositions that are secreted by numerous cell types. Exosomes contain significant bioactive components, including lipids, proteins, mRNA, and miRNA. Exosomes play an important role in regulating cellular signaling and trafficking under both normal physiological and pathological circumstances. A multitude of factors, including thermal stress, ribosomal stress, endoplasmic reticulum stress, and oxidative stress influence the concentrations of exosomal mRNA, miRNA, proteins, and lipids. It has been stated that exosomes derived from stem cells (SCs) modulate a range of stresses by preventing or fostering cell balance. Exosomes derived from SCs facilitate recovery by facilitating cross-cellular communication via the transmission of information in the form of proteins, lipids, and other components. For this reason, exosomes are used as biomarkers to diagnose a wide variety of diseases. The focus of this review is the bioengineering of artificial exosomal cargoes. This process encompasses the control and transportation of particular exosomal cargoes, including but not limited to small molecules, recombinant proteins, immune modulators, and therapeutic medications. Therapeutic approaches of this nature have the potential to deliver therapeutic medications precisely to the intended site for the cure of a variety of disorders. Notably, our attention has been directed towards the therapeutic implementations of exosomes derived from SCs in the cure of cardiovascular ailments, including but not limited to ischemic heart disease, myocardial infarction, sepsis, heart failure, cardiomyopathy, and cardiac fibrosis. In general, researchers employ two methodologies when it comes to exosomal bioengineering. This review aims to explain the function of exosomes derived from SCs in the regulation of stress and present a novel therapeutic approach for cardiovascular disorders.

We designed and performed this meta-analysis to investigate the impact of the application of extracellular small vesicle therapies on regeneration of skin and wound healing. The findings of this study were computed using fixed or random effect models. The mean differences (MDs), and odds ratio (ORs) with their 95% confidence intervals (CIs) were calculated. In this study, 43 publications were included, encompassing 530 animals with artificial wounds. Small extracellular vesicle therapy had a significant greater rate of wound closure (MD, 24.0; 95% CI, 19.98-28.02, P < 0.001), lower scar width (MD, -191.33; 95%CI, -292.26--90.4, P < 0.001), and higher blood vessel density (MD,36.11; 95%CI, 19.02-53.20, P < 0.001) compared to placebo. Our data revealed that small extracellular vesicle therapy had a significantly higher regeneration of skin and healing of wounds based on the results of wound closure rate, lower scar width, and higher blood vessel density compared to placebo. Future studies with larger sample size are needed.

Regenerative effects of sea anemone-derived exosomes on human foreskin fibroblasts (HFFs) were investigated. Water-based extracts from regenerating Aulactinia stella tissue were collected at various time points, and exosomes were extracted after inducing wounds. Both the extract and exosomes were tested on HFF for proliferation and in vitro wound healing. In silico analysis explored protein-protein docking between regenerative exosome proteins and HFF receptors. The MTT (3-(4,5-dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide proliferation assay and in vitro wound healing test of aquatic extract showed proliferative effects on HFF cell lines, with the 60 μg/mL concentration significantly enhancing cell migration. Exosomes were characterised. Exosomes showed a significantly positive effect on cell proliferation and migration at the 50 µg/mL concentration 48 h post-wound induction. In silico analysis revealed potential binding affinities between exosome proteins and HFF receptors. In conclusion, optimised concentrations of A. stella-derived exosomes exhibited positive effects on HFF regeneration and migration, suggesting their potential in accelerating wound healing.

The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties.

In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed in vitro. Additionally, the wound healing capacity of exosomes was evaluated in vivo using a rat full-thickness wound model.

Our in vitro findings revealed that exosomes significantly promoted cell migration. In vivo experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation.

The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in in vitro and in vivo studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings.

Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.

In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events.

Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3 (interferon-induced transmembrane protein 3), which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase.

Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Vascular endothelial inflammation and endothelial dysfunction are the main causes of endothelial injury in Kawasaki disease (KD). Human umbilical cord-derived mesenchymal stem cells (Huc-MSCs) have multiple functions in immune regulation. This study examined whether Huc-MSCs inhibited endothelial inflammation and improved endothelial function in KD through constructing cell and in vivo animal KD vasculitis models. The pyroptosis factor NOD-like receptor protein 3 (NLRP3) was involved in the inflammatory process in the acute phase of KD. After tail vein injection of Huc-MSCs, inflammatory cell infiltration and the expression of pyroptosis-related proteins in the LCWE-induced KD mouse vasculitis model were significantly reduced. In vitro, NLRP3-dependent pyroptosis successfully induced human umbilical vein endothelial cell (HUVEC) damage. Huc-MSCs effectively increased the abilities of impaired HUVECs to proliferate, migrate, invade, and form vessel-like tubes, while inhibiting their apoptosis, suggesting that Huc-MSCs can reduce inflammation and improve vascular endothelial function by inhibiting the NLRP3-dependent pyroptosis pathway in KD, providing a possibility and novel target for KD endothelial injury and dysfunction.

How to effectively repair cutaneous wounds and promote skin rejuvenation has always been a challenging issue for clinical medicine and medical aesthetics. Current conventional medicines exhibit several drawbacks, including limited therapeutic effects, prolonged treatment periods, and high costs. As a novel cell-free therapy, the umbilical cord-derived mesenchymal stem cell (UCMSC) secretome may offer a promising approach for skin regeneration and rejuvenation. The UCMSC secretome is a collection of all proteins secreted by mesenchymal stem cells, including conditioned media, exosomes, and other substances. The UCMSC secretome has numerous abilities to accelerate acute wound healing, including high fibroblast and keratinocyte proliferative activity, pro-angiogenesis, anti-inflammation, anti-fibrosis, and anti-oxidative stress. Its impact on the four stages of wound healing is manifested by inducing the haemostasis phase, inhibiting the inflammation phase, promoting the proliferation phase, and regulating the remodelling phase. Furthermore, it is highly effective in the treatment of chronic wounds, alopecia, aging, and skin homeostasis disturbance. This review focuses on the clinical therapies and application prospects of the UCMSC secretome, encompassing its source, culture, separation, identification, storage, and pretreatment. Additionally, a discussion on the dosage, administration route, efficacy, and biosafety in the clinical situation is presented. This review aims to provide scientific support for the mechanistic investigation and clinical utilisation of the UCMSC secretome in wound healing and skin rejuvenation.

Exosomes and other secretory membrane vesicles are collectively referred to as extracellular vesicles (EVs). Relevant data indicate that stem cell-derived extracellular vesicles (SC-EVs) play a critical role in angiogenesis by transmitting crucial information such as proteins, second messengers, and genetic material between cells. Therefore, this study aimed to map current trends on SC-EVs for angiogenesis and provide directions for future research to advance this important field.

We conducted a thorough search for relevant studies on SC-EVs for angiogenesis from 2003 to 2023 using the Web of Science database. Subsequently, we used VOSviewer and CiteSpace to analyze the collected data.

A total of 2359 relevant publications, which included original articles and reviews, related to the role of SC-EVs in angiogenesis were screened in this study based on the search strategy. China and the United States were leading in this field, with China having a higher output in terms of publications and citations (1172, 43681). Also, the top five universities were located in China, with Shanghai Jiao Tong University having the highest output. Stem Cell Research & Therapy and International Journal of Molecular Sciences, are prominent platforms for researchers in this field to share their findings and advancements, and they had most of published studies on SC-EVs for angiogenesis. The results derived from the cluster analysis suggested that future investigations should predominantly prioritize studying the involvement of SC-EVs in angiogenesis across various diseases, with a specific emphasis on skin wound healing.

In this comprehensive review, global trends in SC-EVs for angiogenesis were analyzed. The analysis of journals, institutions, references, and keywords could assist researchers in deciding on the direction of research. The role of SC-EVs in promoting angiogenesis during wound healing and repair represents an emerging research focus.

Small extracellular vesicles called exosomes play a crucial part in promoting intercellular communication. They act as intermediaries for the exchange of bioactive chemicals between cells, released into the extracellular milieu by a variety of cell types. Within the context of cancer progression, metastasis is a complex process that plays a significant role in the spread of malignant cells from their main site of origin to distant anatomical locations. This complex process plays a key role in the domain of cancer-related deaths. In summary, the trajectory of current research in the field of exosome-mediated metastasis is characterized by its unrelenting quest for more profound understanding of the molecular nuances, the development of innovative diagnostic tools and therapeutic approaches, and the unwavering dedication to transforming these discoveries into revolutionary clinical applications. This unrelenting pursuit represents a shared desire to improve the prognosis for individuals suffering from metastatic cancer and to nudge the treatment paradigm in the direction of more effective and customized interventions.

Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.

Menopausal and postmenopausal women often experience vaginal atrophy due to estrogen deficiency. Mesenchymal stem cell exosomes have emerged as potential therapeutic agents, capable of promoting tissue regeneration and repair.

This study aimed to explore the benefits of exosomes on VK2 cells and the therapeutic effect of topical exosomal hydrogel on atrophic vaginas.

Exosomes were extracted using the high-speed centrifugation method, and their effects on VK2 cell proliferation, migration, and differentiation were observed through co-culture. The menopause model was induced by ovariectomy in rats, followed by the injection of exosome-loaded hydrogel into their vaginas. The treatment's effectiveness was evaluated by measuring vaginal epithelium thickness using HE staining, and assessing vaginal mucosa proliferation and lamina propria angiogenesis using Ki67 and anti-CD31 staining, respectively.

Exosomes significantly promoted VK2 cell proliferation and migration, but had no significant effect on differentiation. The exosome hydrogel increased the expression of Ki67 and CD31, leading to a significant improvement in epithelial thickness.

UcMSC- ex can stimulate the proliferation and migration of VK2 cells, but do not appear to promote differentiation. Topical application of exosome hydrogel enhances vaginal epithelium thickness to a certain degree, offering a promising non-hormonal therapeutic strategy to alleviate vaginal atrophy in postmenopausal women.

To investigate whether human umbilical cord mesenchymal stem cell-derived exosomes combined with gelatin methacryloyl (GelMA) hydrogel are beneficial in promoting healing of laser-injured skin wounds in mice. Supernatants of cultured human umbilical cord mesenchymal stem cells (HUC-MSCs) were collected to obtain human umbilical cord MSC-derived exosomes (HUC-MSCs-Exos), which were combined with GelMA hydrogel complex to treat a mouse fractional laser injury model. The study was divided into PBS group, EX (HUC-MSCs-Exos) group, GEL (GelMA hydrogel) group and EX+GEL (HUC-MSCs-Exos combined with GelMA hydrogel) group. The healing of laser-injured skin in each group was observed by gross view and dermatoscopy, and changes in skin structure, angiogenesis and proliferation-related indexes were observed during the healing process of laser-injured skin in each group. The results of the animal experiments showed that the EX and GEL groups alone and the EL+EX group exhibited less inflammatory response compared to the PBS group. The EX and GEL groups showed marked tissue proliferation and favourable angiogenesis, which promoted the wound healing well. The GEL+EX group had the most significant promotion of wound healing compared to the PBS group. qPCR results showed that the expression levels of proliferation-related factors, including KI67 and VEGF and angiogenesis-related factor CD31, were significantly higher in the GEL+EX group than in the other groups, with a time-dependent effect. The combination of HUC-MSCs-Exos and GelMA hydrogel is beneficial in reducing the early inflammatory response of laser-injured skin in mice and promoting its proliferation and angiogenesis, which in turn promotes wound healing.

The Sonic hedgehog (SHh) signaling pathway is an imperative operating network that helps in regulates the critical events during the development processes like multicellular embryo growth and patterning. Disruptions in SHh pathway regulation can have severe consequences, including congenital disabilities, stem cell renewal, tissue regeneration, and cancer/tumor growth. Activation of the SHh signal occurs when SHh binds to the receptor complex of Patch (Ptc)-mediated Smoothened (Smo) (Ptc-smo), initiating downstream signaling. This review explores how pharmacological modulation of the SHh pathway affects angiogenesis through canonical and non-canonical pathways. The canonical pathway for angiogenesis involves the activation of angiogenic cytokines such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), placental growth factor (PGF), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), stromal cell-derived factor 1α, transforming growth factor-β1 (TGF-β1), and angiopoietins (Ang-1 and Ang-2), which facilitate the process of angiogenesis. The Non-canonical pathway includes indirect activation of certain pathways like iNOS/Netrin-1/PKC, RhoA/Rock, ERK/MAPK, PI3K/Akt, Wnt/β-catenin, Notch signaling pathway, and so on. This review will provide a better grasp of the mechanistic approach of SHh in mediating angiogenesis, which can aid in the suppression of certain cancer and tumor growths.

Acute myocardial infarction (AMI) is a common cardiovascular condition that progressively results in heart failure. In the present study, we have designed to load transforming growth factor beta 3 (TGF-β3) and cardio potential exosomes into the blended polycaprolactone/type I collagen (PCL/COL-1) nanofibrous patch (Exo@TGF-β3@NFs) and examined its feasibility for cardiac repair. The bioactivity of the developed NFs towards the migration and proliferation of human umbilical vein endothelial cells was determined using in vitro cell compatibility assays. Additionally, Exo@TGF-β3/NFs showed up-regulation of genes involved in angiogenesis and mesenchymal differentiations in vitro. The in vivo experiments performed 4 weeks after transplantation showed that the Exo@TGF-β3@NFs had a higher LV ejection fraction and fraction shortening functions. Subsequently, it has been determined that Exo@TGF-β3@NFs significantly reduced AMI size and fibrosis and increased scar thickness. The developed NFs approach will become a useful therapeutic approach for the treatment of AMI.

Mesenchymal stromal cells, commonly referred to as MSCs, are a type of multipotent stem cells that are typically extracted from adipose tissue and bone marrow. In the field of tissue engineering and regenerative medicine, MSCs and their exosomes have emerged as revolutionary tools. Researchers are now devoting greater attention to MSCs because of their ability to generate skin cells like fibroblasts and keratinocytes, as well as their distinctive potential to decrease inflammation and emit pro-angiogenic molecules at the site of wounds. More recent investigations revealed that MSCs can exert numerous direct and indirect antimicrobial effects that are immunologically mediated. Collectively, these antimicrobial properties can remove bacterial infections when the MSCs are delivered in a therapeutic setting. Regardless of the positive therapeutic potential of MSCs for a multitude of conditions, transplanted MSC cell retention continues to be a major challenge. Since MSCs are typically administered into naturally hypoxic tissues, understanding the impact of hypoxia on the functioning of MSCs is crucial. Hypoxia has been postulated to be among the factors determining the differentiation of MSCs, resulting in the production of inflammatory cytokines throughout the process of tissue regeneration and wound repair. This has opened new horizons in developing MSC-based systems as a potent therapeutic tool in oxygen-deprived regions, including anaerobic wound infection sites. This review sheds light on the role of hypoxia-MSCs in the treatment of anaerobic bacterial wound infection in terms of both their regenerative and antimicrobial activities.

As time goes by, the morbidity of diabetes mellitus continues to rise, and the economic burden of diabetic foot ulcers as a common and serious complication of diabetes is increasing. However, currently there is no unified clinical treatment strategy for this complication, and the therapeutic efficacy is unsatisfactory. Recent studies have revealed that biological effects of exosomes involved in multiple stages of the process of wound closure are similar to source cells. Compared with source cells, exosomes possess lowly immunogenicity, highly stability and easily stored, etc. Accumulating evidence confirmed that exosomes promote diabetic wound healing through various pathways such as promoting angiogenesis, collagen fiber deposition, and inhibiting inflammation. The superior therapeutic efficacy of exosomes in accelerating diabetic cutaneous wound healing has attracted an increasing attention. Notably, the molecular mechanisms of exosomes vary among different sources in the chronic wound closure of diabetes. This review focuses on the specific roles and mechanisms of different cell- or tissue-derived exosomes relevant to wound healing. Additionally, the paper provides an overview of the current pre-clinical and clinical applications of exosomes, illustrates their special advantages in wound repair. Furthermore, we discuss the potential obstacles and various solutions for future research on exosomes in the management of diabetic foot ulcer. The aim is to offer novel insights and approaches for the treatment of diabetic foot ulcer.

The use of biomaterials in delivering CRISPR/Cas9 for gene therapy in infectious diseases holds tremendous potential. This innovative approach combines the advantages of CRISPR/Cas9 with the protective properties of biomaterials, enabling accurate and efficient gene editing while enhancing safety. Biomaterials play a vital role in shielding CRISPR/Cas9 components, such as lipid nanoparticles or viral vectors, from immunological processes and degradation, extending their effectiveness. By utilizing the flexibility of biomaterials, tailored systems can be designed to address specific genetic diseases, paving the way for personalized therapeutics. Furthermore, this delivery method offers promising avenues in combating viral illnesses by precisely modifying pathogen genomes, and reducing their pathogenicity. Biomaterials facilitate site-specific gene modifications, ensuring effective delivery to infected cells while minimizing off-target effects. However, challenges remain, including optimizing delivery efficiency, reducing off-target effects, ensuring long-term safety, and establishing scalable production techniques. Thorough research, pre-clinical investigations, and rigorous safety evaluations are imperative for successful translation from the laboratory to clinical applications. In this review, we discussed how CRISPR/Cas9 delivery using biomaterials revolutionizes gene therapy and infectious disease treatment, offering precise and safe editing capabilities with the potential to significantly improve human health and quality of life.

Wound repair is a complex problem for both clinical practitioners and scientific investigators. Conventional approaches to wound repair have been associated with several limitations, including prolonged treatment duration, high treatment expenses, and significant economic and psychological strain on patients. Consequently, there is a pressing demand for more efficacious and secure treatment modalities to enhance the existing treatment landscapes. In the field of wound repair, cell-free therapy, particularly the use of mesenchymal stem cell-derived exosomes (MSC-Exos), has made notable advancements in recent years. Exosomes, which are small lipid bilayer vesicles discharged by MSCs, harbor bioactive constituents such as proteins, lipids, microRNA (miRNA), and messenger RNA (mRNA). These constituents facilitate material transfer and information exchange between the cells, thereby regulating their biological functions. This article presents a comprehensive survey of the function and mechanisms of MSC-Exos in the context of wound healing, emphasizing their beneficial impact on each phase of the process, including the regulation of the immune response, inhibition of inflammation, promotion of angiogenesis, advancement of cell proliferation and migration, and reduction of scar formation.

Tissue engineered skin and its substitutes have a promising future in wound healing. However, enabling fast formation of blood vessels during the wound healing process is still a huge challenge to the currently available wound substitutes. In this work, active mesoporous bioglass nanoparticles with a high specific surface area and doped with strontium (Sr) were fabricated for rapid microvascularization and wound healing. The as-prepared bioglass nanoparticles with Sr ions significantly promoted the proliferation of fibroblasts and microvascularization of human umbilical vein endothelial cells in vitro. Silk fibroin sponges encapsulating the nanoparticles accelerated wound healing by promoting the formation of blood vessels and epithelium in vivo. This work provides a strategy for the design and development of active biomaterials for enhancing wound healing by rapid vascularization and epithelial reconstruction.

Wound healing is a complicated biological process that leads to the regeneration of damaged skin tissue. Determining the methods to promote wound healing has become a hot topic in medical cosmetology and tissue repair research. Mesenchymal stem cells (MSCs) are a group of stem cells with the potential of self-renewal and multi-differentiation. MSCs transplantation has a broad application prospect in wound healing therapy. Many studies have demonstrated that the therapeutic capacity of MSCs is mainly mediated by paracrine actions. Exosomes (EXOs), which are nanosized vesicles carrying a variety of nucleic acids, proteins and lipids, are an important component of paracrine secretion. It has been demonstrated that exosomal microRNAs (EXO-miRNAs) play a key role in the function of exosomes.

In this review, we focus on current research on miRNAs from MSC-derived exosomes (MSC-EXO miRNAs) in terms of sorting, releasing and function and their effects on inflammation regulation, epidermal cell function, fibroblast function, and extracellular matrix formation. At last, we discuss the current attempts to improve the treatment of MSC-EXO-miRNAs.

Many studies have demonstrated that MSC-EXO miRNAs play a key role in promoting wound healing. They have been shown to regulate inflammation response, enhance epidermal cell proliferation and migration, stimulate fibroblast proliferation and collagen synthesis, and regulate extracellular matrix formation. Besides, there have been a number of strategies developed to promote MSC-EXO and MSC-EXO miRNAs for wound healing treatment.

Utilizing the association of exosomes from MSCs with miRNAs may be a promising strategy to promote trauma healing. MSC-EXO miRNAs may provide a new approach to promote wound healing and improve the quality of life for patients with skin injuries.

Regeneration is a complex process affected by many elements independent or combined, including inflammation, proliferation, and tissue remodeling. Stem cells is a class of primitive cells with the potentiality of differentiation, regenerate with self-replication, multidirectional differentiation, and immunomodulatory functions. Stem cells and their cytokines not only inextricably linked to the regeneration of ectodermal and skin tissues, but also can be used for the treatment of a variety of chronic wounds. Stem cells can produce exosomes in a paracrine manner. Stem cell exosomes play an important role in tissue regeneration, repair, and accelerated wound healing, the biological properties of which are similar with stem cells, while stem cell exosomes are safer and more effective. Skin and bone tissues are critical organs in the body, which are essential for sustaining life activities. The weak repairing ability leads a pronounced impact on the quality of life of patients, which could be alleviated by stem cell exosomes treatment. However, there are obstacles that stem cells and stem cells exosomes trough skin for improved bioavailability. This paper summarizes the applications and mechanisms of stem cells and stem cells exosomes for skin and bone healing. We also propose new ways of utilizing stem cells and their exosomes through different nanoformulations, liposomes and nanoliposomes, polymer micelles, microspheres, hydrogels, and scaffold microneedles, to improve their use in tissue healing and regeneration.

Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed involving studies conducted and published over the past five years. A PubMed search was performed for English-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed that exosome-based treatments improve wound healing by increasing angiogenesis, reepithelization, collagen deposition, and decreasing scar formation. Furthermore, there was significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.

Although the application of stem cells to chronic wounds emerged as a candidate therapy in the previous century, the mechanism of action remains unclear. Recent evidence has implicated secreted paracrine factors in the regenerative properties of cell-based therapies. In the last two decades, considerable research advances involving the therapeutic potential of stem cell secretomes have expanded the scope of secretome-based therapies beyond stem cell populations. In this study, we review the modes of action of cell secretomes in wound healing, important preconditioning strategies for enhancing their therapeutic efficacy, and clinical trials on secretome-based wound healing.

Extracellular vesicles (EVs) are cell-derived nano-sized lipid membranous structures that modulate cell-cell communication by transporting a variety of biologically active cellular components. The potential of EVs in delivering functional cargos to targeted cells, their capacity to cross biological barriers, as well as their high modification flexibility, make them promising drug delivery vehicles for cell-free therapies. Mesenchymal stromal cells (MSCs) are known for their great paracrine trophic activity, which is largely sustained by the secretion of EVs. MSC-derived EVs (MSC-EVs) retain important features of the parental cells and can be bioengineered to improve their therapeutic payload and target specificity, demonstrating increased therapeutic potential in numerous pre-clinical animal models, including in the treatment of cancer and several degenerative diseases. Here, we review the fundamentals of EV biology and the bioengineering strategies currently available to maximize the therapeutic value of EVs, focusing on their cargo and surface manipulation. Then, a comprehensive overview of the methods and applications of bioengineered MSC-EVs is presented, while discussing the technical hurdles yet to be addressed before their clinical translation as therapeutic agents.

Wound healing is a dynamic and complicated process containing overlapping phases. Presently, definitive therapy is not available, and the investigation into optimal wound care is influenced by the efficacy and cost-effectiveness of developing therapies. Accumulating evidence demonstrated the potential role of mesenchymal stem/stromal cell (MSC) therapy in several tissue injuries and diseases due to their high proliferation and differentiation abilities along with an easy collection procedure, low tumorigenesis, and immuno-privileged status. MSCs have also accelerated wound repair in all phases through their advantageous properties, such as accelerating wound closure, improving re-epithelialization, elevating angiogenesis, suppressing inflammation, and modulating extracellular matrix (ECM) remodeling. In addition, the beneficial therapeutic impacts of MSCs are largely associated with their paracrine functions, including extracellular vesicles (EVs). Exosomes and microvesicles are the two main subgroups of EVs. These vesicles are heterogeneous bilayer membrane structures that contain several proteins, lipids, and nucleic acids. EVs have emerged as a promising alternative to stem cell-based therapies because of their lower immunogenicity, tumorigenicity, and ease of management. MSCs from various sources have been widely investigated in skin wound healing and regeneration. Considering these features, in this review, we highlighted recent studies that the investigated therapeutic potential of various MSCs and MSC-EVs in skin damages and wounds.