Atherosclerosis (AS) is a disease with high global incidence and mortality rates. Currently, the treatment of AS in clinical practice carries a high risk of adverse effects and toxic side effects. The pretreatment of mesenchymal stem cells (MSCs) with drugs may enhance the bioactivity of MSC‑derived exosomes (MSC‑exos), which could be a promising candidate for inhibiting the progression of AS. The aim of the present study was to investigate the ability of exos derived from baicalin‑preconditioned MSCs (Ba‑exos) to exhibit an inhibitory effect on AS progression and to explore the potential molecular mechanisms. Exos were isolated from untreated MSCs and MSCs pretreated with Ba, and were characterized using transmission electron microscopy, nanoparticle tracking analysis and western blotting. Subsequently, Cell Counting Kit‑8 and Transwell assays, reverse transcription‑quantitative PCR, immunofluorescence, western blotting and ELISA were used to evaluate the effects of Ba‑exos on AS, and the possible molecular mechanisms. Oil Red O and Masson staining were used to assess AS pathological tissue in a high‑fat diet‑induced mouse model of AS. Notably, MSC‑exos and Ba‑exos were successfully isolated. Compared with MSC‑exos, Ba‑exos demonstrated superior inhibitory effects on the viability and migration, and the levels of inflammatory factors in oxidized low‑density lipoprotein (ox‑LDL)‑induced vascular smooth muscle cells (VSMCs). Additionally, compared with MSC‑exos, Ba‑exos significantly inhibited NF‑κB activation by upregulating sirtuin 1 (SIRT1), thereby suppressing inflammation in ox‑LDL‑induced VSMCs to a greater extent. In mice with high‑fat diet‑induced AS, Ba‑exos exhibited the ability to inhibit AS plaque formation and to alleviate AS progression by reducing the levels of inflammatory factors compared with MSC‑exos; however, the difference was not significant. In conclusion, Ba‑exos may serve as a potential strategy for treating AS by regulating the SIRT1/NF‑κB signaling pathway to suppress inflammation.

In this article, we revisit an article, which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells (MSCs) for targeted delivery of gemcitabine in pancreatic cancer treatment. The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells. The biocompatibility, targeting specificity, and low immunogenicity of exosomes render them as optimal carriers for drug delivery, enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects, thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy. However, the clinical application of exosome drug delivery platforms in oncology still presents challenges, necessitating further optimization to ensure their stability and efficacy. This study focuses on elucidating the advantages of exosomes as a drug delivery platform, exploring the utilization of MSC-derived exosomes in oncology therapy, and discussing their potential and future directions in cancer treatment.

Osteonecrosis of the femoral head (ONFH) is a destructive bone disease, and overuse of alcohol is one of the major contributing factors. Although mesenchymal stem cells (MSCs) and their exosomes have been reported to attenuate ONFH, the potential mechanisms of alcohol-induced ONFH (AONFH) are unclear. Here, we isolated and identified human umbilical cord MSCs-derived exosomal (hucMSCs-exos) miR-25-3p. We observed that hucMSCs-exos transferred miR-25-3p into bone marrow stem cells (BMSCs). HucMSCs-exos miR-25-3p increased cell viability, osteogenic differentiation, and inhibited apoptosis of alcohol-treated BMSCs and AONFH rat model. Mechanically, hucMSCs-exos upregulated miR-25-3p expression in BMSCs by repressing miR-25-3p DNA methylation, and DNA methylation inhibitor 5-Aza-2-deoxycytidine (DAC) ameliorated AONFH. Besides, miR-25-3p suppressed gremlin 1 (GREM1) expression, and upregulation of GREM1 restored the inhibition of hucMSCs-exos on AONFH. Therefore, we determined that hucMSCs-exos miR-25-3p alleviated AONFH by inhibiting miR-25-3p DNA methylation and GREM1 expression, which may help identify novel biomarkers, diagnostic and therapeutic targets.

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 aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections.

An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1).

RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNFα signaling via NFκB (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months.

The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules.

Chitosan is an excellent carrier material for bioactive substances, and its binding ability is affected by the pH value of surrounding environments. Healthy skin is maintained in a slightly acidic environment, whereas the wound healing environment is normally neutral or slightly alkaline. In the present study, the authors proposed developing a thermally stable bioactive chitosan scaffold (T-CS) with pH-responsive exosome adsorption and release functions to promote wound healing. Our results revealed that T-CS could automatically capture exosomes from human umbilical cord mesenchymal stem cells in an acidic environment and release them in alkaline or neutral environments. The exosomes separated by T-CS and the traditional ultracentrifugation (UC) method exhibited similar size and protein markers. Furthermore, the exosomal biological activities of the T-CS (T-CS-E) and UC groups exhibited similar anti-inflammatory, proproliferation, promigration, and proendothelial cell-tube formation effects on human umbilical vein endothelial cells. Similar results were achieved in a mouse model by sustainably releasing exosomes. T-CS-E could facilitate wound healing by enhancing cell proliferation, inhibiting wound inflammation, and promoting vascularization. Therefore, this study developed a T-CS scaffold that integrates exosome isolation and application for wound healing, laying the foundation for future clinical use.

With the exacerbation of the aging population trend, a series of neurodegenerative diseases caused by brain aging have become increasingly common, significantly impacting the daily lives of the elderly and imposing heavier burdens on nations and societies. Brain aging is a complex process involving multiple mechanisms, including oxidative stress, apoptosis of damaged neuronal cells, chronic inflammation, and mitochondrial dysfunction, and research into new therapeutic strategies to delay brain aging has gradually become a research focus in recent years. Mesenchymal stem cells (MSCs) have been widely used in cell therapy due to their functions such as antioxidative stress, anti-inflammation, and tissue regeneration. However, accompanying safety issues such as immune rejection, tumor development, and pulmonary embolism cannot be avoided. Studies have shown that using exosome derived from mesenchymal stem cells (MSC-Exo) for the treatment of neurodegenerative diseases is a safe and effective method. It not only has the therapeutic effects of stem cells but also avoids the risks associated with cell therapy. Therefore, exploring new therapeutic strategies to delay normal brain aging from the mechanism of MSC-Exo in the treatment of neurodegenerative diseases is feasible. This review summarizes the characteristics of MSC-Exo and their clinical progress in the treatment of neurodegenerative diseases, aiming to explore the possibility and potential mechanisms of MSC-Exo in reversing brain aging.

There's a scarcity of drugs effective against nonalcoholic steatohepatitis (NASH). Exosomes from Human umbilical cord mesenchymal stem cells (huc-MSCs) show potential in managing glycolipid metabolism and the immune response. Therefore, further investigations are required to explore their application in NASH and the underlying mechanisms.

C57BL/6J mice were fed with a western diet for 12 weeks to induce NASH, and huc-MSCs exosomes (MSCs-exo) were administered during the feeding period. The effect of MSCs-exo was evaluated by monitoring changes in body weight, fat distribution, blood glucose, and insulin levels, and analyzing pathological alterations in liver tissue. Mechanism investigations were carried out using flow cytometry, immunofluorescence staining, and other experimental techniques.

MSCs-exo could reduce liver fat, inflammation, fibrosis, and improved metabolism to alleviate the progression of NASH. Besides, MSCs-exo could decrease macrophage accumulation in the liver, encouraging M2 over M1 macrophage polarization. Furthermore, our study found that MSCs-exo had a high expression of miR-24-3p, which may regulate macrophage polarization by targeting the interferon-stimulated genes (STING) gene in macrophages, with its overexpression amplifying MSCs-exo's NASH benefits.

These findings suggest that the therapeutic effect of MSCs-exo on NASH may be attributed to the regulation of macrophage M2 polarization through miR-24-3p targeting STING. This provides a scientific basis for future clinical application.

Diabetic foot ulcers (DFUs) are chronic wounds and a common complication of diabetes. A promising strategy in the treatment of DFUs involves the use of stem cell derivatives, such as small extracellular vesicles (sEVs), which can enhance cell proliferation and reduce inflammation while avoiding immunogenic responses. In this study, we evaluated the ability of adipose mesenchymal stem cell- (ASC)-derived sEVs to enhance the proliferation of human fibroblasts, which play a crucial role in wound regenerative processes. To mimic the inflammatory environment of DFUs, fibroblasts were cultured into the gellan gum (GG) modified with ethylenediamine (EDA) hydrogel scaffolds loaded with ASC-derived sEVs, under pro-inflammatory cytokines. Our comparative analysis demonstrated that sEVs loaded in GG-EDA hydrogel improved fibroblast viability in pro-inflamed conditions while retaining the anti-inflammatory and immunomodulatory properties of their cells of origin. By modulating the gene expression profile of fibroblasts to promote cell proliferation, wound healing and re-epithelialization, our system presents a promising therapeutic strategy for DFU healing.

Research has unveiled the remarkable properties of extracellular vesicles derived from mesenchymal stromal cells (MSCs), particularly in promoting wound healing, aiding re-epithelialization, revitalizing aging skin, and inhibiting hyperpigmentation. However, investigations into the potential of small extracellular vesicles from umbilical cord-derived MSCs (UC-MSC-sEVs) in reducing scarring and preventing hyperpigmentation remain limited. Therefore, this study aims to evaluate the impact of UC-MSC-sEVs on the synthesis of the skin's extracellular matrix (ECM) and pigmentation using in vitro models.

The study investigated the impact of characterized UC-MSC-sEVs on various aspects including the proliferation, migration, antioxidant activity, and ECM gene expression of human dermal fibroblasts (HDF). Additionally, the effects of UC-MSC-sEVs on the proliferation, melanin content, and tyrosinase (TYR) activity of human melanoma cells (MNT-1) were examined. Furthermore, ex vivo models were employed to evaluate the skin permeation of PKH26-labelled UC-MSC-sEVs.

The findings indicated that a high concentration of UC-MSC-sEVs positively influenced the proliferation of HDF. However, no changes in cell migration rate were observed. While the expressions of collagen type 1 and type 3 remained unaffected by UC-MSC-sEVs treatment, there were dose-dependent increases in the gene expressions of fibronectin, matrix metallopeptidase (MMP) 1, and MMP 3. Furthermore, UC-MSC-sEVs treatment did not impact the antioxidative superoxide dismutase (SOD) expression in HDF. Although UC-MSC-sEVs did not alter the proliferation of MNT-1 cells, it did result in a dose-dependent reduction in melanin synthesis without affecting TYR activity. However, when it was applied topically, UC-MSC-sEVs failed to penetrate the skin barrier and remained localized within the stratum corneum layer even after 18 hours.

These results highlight the potential of UC-MSC-sEVs in stimulating HDF proliferation, regulating ECM synthesis, and reducing melanin production. This demonstrates the promising application of UC-MSC-sEVs in medical aesthetics for benefits such as scar reduction, skin rejuvenation, and skin lightening.

Multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS), is characterized by inflammation, demyelination, and neurodegeneration, leading to diverse clinical manifestations such as fatigue, sensory impairment, and cognitive dysfunction. Current pharmacological treatments primarily target immune modulation but fail to arrest disease progression or entirely reverse CNS damage. Mesenchymal stem cell (MSC) therapy offers a promising alternative, leveraging its immunomodulatory, neuroprotective, and regenerative capabilities. This review provides an in-depth analysis of MSC mechanisms of action, including immune system regulation, promotion of remyelination, and neuroregeneration. It examines preclinical studies and clinical trials evaluating the efficacy, safety, and limitations of MSC therapy in various MS phenotypes. Special attention is given to challenges such as delivery routes, dosing regimens, and integrating MSCs with conventional therapies. By highlighting advancements and ongoing challenges, this review underscores the potential of MSCs to revolutionize MS treatment, paving the way for personalized and combinatory therapeutic approaches.

The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In recent years, plant-to-mammal regulation has provided an effective approach for chronic wound management, but the development of effective plant-based treatments remains challenging. The development of exosomes from Chinese herbs is promising for wound healing. In this study, plant exosomes derived from lemons (Citrus limon) were extracted, and their biological efficacy was verified. Lemon exosomes regulated the polarization reprogramming of macrophages, promoted the proliferation and migration of vascular endothelial cells and fibroblasts, and thus promoted the healing of diabetic wounds. To solve the problems of continuous drug delivery and penetration depth, Lemon Exosomes were loaded into a hydrogel constructed of Gelatin Methacryloyl (GelMA) and Dialdehyde Starch (DAS) that closely fits to the skin, absorbs water, swells, and is moist and breathable, effectively promoting the sustained and slow release of exosomes and resulting in excellent performance for diabetic wound healing. Our GelMA-DAS-Lemon Exosomes hydrogel (GelMA/DAS/Exo hydrogel) patch represents a potentially valuable option for repairing diabetic wounds in clinical applications.

Acute lung injury (ALI) is a critical clinical disease caused by direct factors (inhalation injury, gastroesophageal reflux, etc.) or indirect factors (including infection, sepsis, burn, shock, trauma, acute pancreatitis, fat embolism, drug overdose, etc.). ALI is characterized mainly by diffuse interstitial and alveolar edema caused by an uncontrolled inflammatory response and damage to the alveoli-capillary barrier and has very high morbidity and mortality rates. Currently, there is no effective treatment strategy other than mechanical ventilation, fluid management or other supportive treatments. Exosomes are nanovesicle-like vesicles with double-membrane structures detached from the cell membrane or secreted by cells. These vesicles can be used as drug carriers because of their unique biological properties, such as anti-inflammatory, anti-apoptotic, pro-cell growth and immunomodulatory functions, and have been applied in the treatment of ALI in recent years. In this study, the mechanism and pathophysiological characteristics of ALI were first systematically described. The different cellular sources and characteristics of exosomes are summarized, and their functions and value as drug carriers in the treatment of ALI are discussed, as are the challenges that may be faced in the treatment of ALI with exosomes.

Although cancer therapy has significantly advanced in recent decades, patients and healthcare professionals are still quite concerned about adverse effects due to the non-targeted nature of currently used chemotherapeutics. Results obtained in a large number of recently published experimental studies indicated that mesenchymal stem-cell-derived exosomes (MSC-Exos), due to their biocompatibility, ability to cross biological barriers, and inherent targeting capabilities, could be used as a promising drug-delivery system for anti-cancer therapies. Their lipid bilayer protects cargo of anti-cancer drugs, making them excellent candidates for the delivery of therapeutic agents. MSC-Exos could be engineered to express ligands specific for tumor cells and, therefore, could selectively deliver anti-cancer agents directly in malignant cells, minimizing side effects associated with chemotherapeutic-dependent injury of healthy cells. MSC-Exos can carry multiple therapeutic agents, including anti-cancer drugs, micro RNAs, and small bioactive molecules, which can concurrently target multiple signaling pathways, preventing tumor growth and progression and overcoming resistance of tumor cells to many standard chemotherapeutics. Accordingly, in this review article, we summarized current knowledge and future perspectives about the therapeutic potential of MSCs-Exos in anti-cancer treatment, opening new avenues for the targeted therapy of malignant diseases.

Acute lung injury being one of the earliest and most severe complications during sepsis and macrophages play a key role in this process. To investigate the regulatory effects and potential mechanisms of adipose mesenchymal stem cell derived-exosomes (ADSC-exo) on macrophages and septic mice, ADSCs-exo was administrated to both LPS-induced macrophage and cecal ligation and puncture (CLP) induced sepsis mice. ADSCs-exo was confirmed to inhibit M1 polarization of macrophages and to reduce excessive inflammation. The use of ADSCs-exo in CLP mice and in LPS-induced macrophages relieved oxidative stress, cellular damage, and acute lung injury. During this process, ADSCs-exo increased the nuclear translocation of Nrf2, significantly upregulating the activation of the antioxidant pathway Nrf2/HO-1. Concurrently, they enhanced the expression of SIRT1 in macrophages. Further SIRT1 interference experiments demonstrated that ADSCs-exo mitigated macrophage inflammatory responses and LPS-induced ferroptosis by upregulating SIRT1. In the LPS-induced macrophage model, after SIRT1 was interfered with, ADSCs-exo failed to upregulate the Nrf2/HO-1 signaling pathway, leading to enhanced ferroptosis. Finally, in a CLP sepsis mouse model with myeloid-specific SIRT1 knockout, ADSCs-exo was observed to reduce lung tissue injury, oxidative stress damage, and ferroptosis. Still, these beneficial effects were reversed due to the myeloid-specific knockout of SIRT1, while co-administration of a ferroptosis inhibitor rescued this situation, alleviating lung injury and significantly reducing tissue levels of oxidative stress. In conclusion, this study elucidated a novel potential therapeutic mechanism wherein ADSCs-exo upregulates the levels of SIRT1 in macrophages through a non-delivery approach.

Skin regeneration, repair, and the promotion of hair growth are intricate and dynamic processes essential for preserving the overall health, functionality, and appearance of both skin and hair. These processes involve a coordinated interplay of cellular activities and molecular signaling pathways that ensure the maintenance and restoration of skin integrity and hair vitality. Recent advancements in regenerative medicine have underscored the significant role of mesenchymal stem cell (MSC)-derived exosomes as key mediators in these processes. Exosomes, emerging as a promising cell-free therapy in tissue engineering, hold substantial potential due to their ability to influence various biological functions. This review explores the mechanisms by which MSC-derived exosomes facilitate skin regeneration and repair, and hair growth, their therapeutic applications, and the future research directions in this emerging field.

At present, the treatment for allergic rhinitis (AR) is only limited to symptom relief, and AR is not able be cured. It is important to find new therapeutic regimens for AR.

To explore the effect of adipose mesenchymal stem cell-derived exosomes (AMSC-exos) on AR in mice.

Primary human AMSCs were cultured up to fourth or fifth passage AMSCs which were used to extract AMSC-exos by ultracentrifugation. The AMSC-exos were identified in size, morphology and surface marker proteins. AR mouse models were made, and then effects of the AMSC-exos on AR mouse models were observed by injection of AMSC-exos into their tail veins. A total of 21 mice were divided into normal mice with injection of phosphate buffered saline (PBS) group (Normal + PBS group, 7 mice), AR mice with injection of AMSC-exos group (AR + AMSC-exos group, 7 mice) and AR mice with injection of PBS (AR + PBS group, 7 mice). After injection of AMSC-exos and PBS, symptoms were observed in mice and inflammatory factors including IL-4, IL-5, IFN- γ and Ig-E were determined. Mice were sacrificed, nasal mucosa was collected for HE staining and qRT-PCR.

After injection of AMSC-exos, compared with the AR + PBS group, symptoms were significantly improved, inflammatory factor levels were significantly decreased, disturbed and thickened mucosal layer was relieved, and the numbers of goblet cells and eosinophils were reduced in the AR + AMSC-exos group.

AMSC-exos can improve symptoms and inflammatory level in the AR mice.

Diabetes mellitus (DM) is a fatal metabolic disease characterized by persistent hyperglycemia. In recent studies, mesenchymal stem cell (MSC)-derived exosomes, which are being investigated clinically as a cell-free therapy for various diseases, have gained attention due to their biomimetic properties that closely resemble natural cellular communication systems. These MSC-derived exosomes inherit the regenerative and protective effects from MSCs, inducing pancreatic β-cell proliferation and inhibiting apoptosis, as well as ameliorating insulin resistance by suppressing the release of various inflammatory cytokines. Consequently, MSC-derived exosomes have attracted attention as a novel treatment for DM as an alternative to stem cell therapy. In this review, we will introduce the potential of MSC-derived exosomes for the treatment of DM by discussing the studies that have used MSC-derived exosomes to treat DM, which have shown therapeutic effects in both type 1 and type 2 DM.

Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights the unique properties of EVs, such as their biocompatibility, capacity to cross the blood-brain barrier (BBB), and potential for therapeutic cargo loading, including that of enzymes and genetic material. Current therapies for LSDs, like enzyme replacement therapy (ERT), often fail to address neurological symptoms due to their inability to cross the BBB. EVs offer a viable alternative, allowing for targeted delivery to the CNS and improving therapeutic outcomes. We discuss recent advancements in the engineering and modification of EVs to enhance targeting, circulation time and cargo stability, and provide a detailed overview of their application in LSDs, such as Gaucher and Fabry diseases, and Sanfilippo syndrome. Despite their potential, challenges remain in scaling production, ensuring isolation purity, and meeting regulatory requirements. Future developments will focus on overcoming these barriers, paving the way for the clinical translation of EV-based therapies in LSDs and other CNS disorders.

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, with a high rate of disability and mortality. Due to the complicated pathological process of SCI, there is no effective clinical treatment strategy at present. Although mesenchymal stem cells (MSCs) are effective in the treatment of SCI, their application is limited by factors such as low survival rate, cell dedifferentiation, tumorigenesis, blood-brain barrier, and immune rejection. Fortunately, there is growing evidence that most of the biological and therapeutic effects of MSCs may be mediated by the release of paracrine factors, which are extracellular vesicles called exosomes. Exosomes are small endosomal vesicles with bilaminar membranes that have recently been recognized as key mediators for communication between cells and tissues through the transfer of proteins, lipids, nucleic acids, cytokines, and growth factors. Mesenchymal stem cell-derived exosomes (MSC-exos) play a critical role in SCI repair by promoting angiogenesis and axonal growth, regulating inflammation and immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be used to transport genetic material or drugs to target cells, and their relatively small size allows them to permeate the blood-brain barrier. Studies have demonstrated that some exosomal miRNAs derived from MSCs play a significant role in the treatment of SCI. In this review, we summarize recent research advances in MSC-exos and exosomal miRNAs in SCI therapy to better understand this emerging cell-free therapeutic strategy and discuss the advantages and challenges of MSC-exos in future clinical applications.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm that typically manifests with subtle clinical manifestations in its early stages and frequently eludes diagnosis until the advanced phases of the disease. The limited therapeutic options available for PDAC significantly contribute to its high mortality rate, highlighting the urgent need for novel biomarkers capable of effectively identifying early clinical manifestations and facilitating precise diagnosis. The pivotal role of cellular exosomes in both the pathogenesis and therapeutic interventions for PDAC has been underscored. Furthermore, researchers have acknowledged the potential of exosomes as targeted drug carriers against regulatory cells in treating PDAC. The present article aims to provide a comprehensive review encompassing recent advancements in utilizing exosomes for elucidating mechanisms underlying disease development, patterns of metastasis, diagnostic techniques and treatment strategies associated with PDAC.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition resulting from impaired oxygen and blood flow to the brain during birth, leading to neuroinflammation, neuronal apoptosis, and long-term neurological deficits. Despite the use of therapeutic hypothermia, current treatments remain inadequate in fully preventing brain damage. Recent advances in mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) offer a novel, cell-free therapeutic approach, as these EVs can cross the blood-brain barrier (BBB) and deliver functional microRNAs (miRNAs) to modulate key pathways involved in inflammation and neuroprotection. This review examines how specific miRNAs encapsulated in MSC-EVs-including miR-21, miR-124, miR-146, and the miR-17-92 cluster-target the complex inflammatory responses that drive HIE pathology. By modulating pathways such as NF-κB, STAT3, and PI3K/Akt, these miRNAs influence neuroinflammatory processes, reduce neuronal apoptosis, and promote tissue repair. The aim is to assess the therapeutic potential of miRNA-loaded MSC-EVs in mitigating inflammation and neuronal damage, thus addressing the limitations of current therapies like therapeutic hypothermia.

Exosomes are extracellular vesicles, composed of a phospholipid bilayer, that are primarily derived from stem cells. The contents of exosomes can be incorporated into the tissue in which they are introduced, which presents a unique therapeutic option.

Exosomes have been investigated as a treatment for a number of medical ailments, but the literature supporting these indications is inconclusive. In addition, much of the study on exosomes and their uses has been recently completed. Thus, this review summarizes the efficacy and implications of exosomes in the treatment of different dermatologic conditions.

A literature review surrounding the use of exosomes for multiple medical dermatological conditions was conducted. Additionally, we present numerous practical cases in which patients had been treated with exosomes.

Overall, the success of exosomes in treating medical dermatologic conditions demonstrated varying efficacy in the literature, but the preliminary evidence is generally positive. The patient cases also showed satisfactory clinical outcomes but further studies and cases will be necessary to fully characterize the efficacy of exosomes and the ideal modalities for their application, including formulation, mode of distribution, and frequency of treatment.

Exosomes may serve as an effective treatment option for wound healing, reconstruction of skin flaps, radiation dermatitis, acne vulgaris, psoriasis, atopic dermatitis, allergic contact dermatitis, lichen simplex chronicus, vulvar lichen sclerosis, systemic sclerosis, systemic lupus erythematosus, and vitiligo although additional studies are needed to confirm their efficacy and safety.

Mesenchymal stem cells (MSCs) derived from gestational tissues offer a promising avenue for prenatal intervention in congenital malformations although their application is hampered by concerns related to cellular plasticity and the need for invasive, high-risk surgical procedures. Here, we present naturally occurring exosomes (EXOs) isolated from amniotic fluid-derived MSCs (AF-MSCs) and their mimetic analogs (MIMs) as viable, reproducible, and stable alternatives. These nanovesicles present a minimally invasive therapeutic option, addressing the limitations of MSC-based treatments while retaining therapeutic efficacy.

MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. A physicochemical, structural, and molecular comparison was conducted with exosomes (EXOs) released from the same batch of cells. Additionally, their distribution patterns in female mice were evaluated following in vivo administration, along with an assessment of their safety profile throughout gestation in a mouse strain predisposed to neural tube defects (NTDs). The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake in two different cell types(fibroblasts, and macrophages) and mRNA functionality overtime in an in vitro experimental setting as well as in an ex vivo, whole embryo culture using pregnant C57BL6 dams.

Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a threefold greater yield. Biodistribution patterns following intraperitoneal administration were comparable between the two particle types, with the uterus being among targeted organs. No toxic effects were observed in the dams during gestation, nor were there any malformations or significant differences in the number of viable versus dead fetuses detected. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein in macrophages and fibroblasts. An ex-vivo whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.

The present data confirms the potential application of EXOs and MIMs as suitable tools for prevention and treatment of NTDs and proposes MIMs as prospective vehicles to prevent congenital malformations caused by in utero exposure to drugs.

Complete wound healing without scar formation has attracted increasing attention, prompting the development of various strategies to address this challenge. In clinical settings, there is a growing preference for emerging biomedical technologies that effectively manage fibrosis following skin injury, as they provide high efficacy, cost-effectiveness, and minimal side effects compared to invasive and costly surgical techniques. This review gives an overview of the latest developments in advanced biomedical technologies for scarless wound management. We first introduce the wound healing process and key mechanisms involved in scar formation. Subsequently, we explore common strategies for wound treatment, including their fabrication methods, superior performance and the latest research developments in this field. We then shift our focus to emerging biomedical technologies for scarless wound healing, detailing the mechanism of action, unique properties, and advanced practical applications of various biomedical technology-based therapies, such as cell therapy, drug therapy, biomaterial therapy, and synergistic therapy. Finally, we critically assess the shortcomings and potential applications of these biomedical technologies and therapeutic methods in the realm of scar treatment.

 : Among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organs appears promising. We hypothesized that using a cell therapy based on extracellular vesicles (EVs) derived from urine progenitor cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR-related kidney damage. We isolated and characterized porcine UPCs and their extracellular vesicles (EVs). Then these were used in an ex vivo porcine kidney preservation model. Kidneys were subjected to warm ischemia (32 min) and then preserved by hypothermic machine perfusion (HMP) for 24 h before 5 h of normothermic machine perfusion (NMP). Three groups were performed (n = 5-6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/EVs + NMP/vehicle, Group 3 (G3): HMP/EVs + NMP/EVs. Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. However, cell damage markers (LDH, ASAT) were decreased in G3 compared with G1, and G3 kidneys displayed a preserved tissue integrity with reduced tubular dilatation and inflammation notably. However, renal function indicators such as creatinine clearance measured for 5 h of normothermic perfusion or NGAL perfusate's level were not modified by EVs injection. Regarding perfusate analysis, metabolomic analyses and cytokine quantification showed an immunomodulation signature in G3 compared with G1 and highlighted potential metabolic targets. In vitro, EVs as well as perfusates from G3 partially recovered endothelial cell metabolic activity after hypoxia. Finally, RNA-seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of EVs therapy. We showed the feasibility/efficacy of UPC-EVs for hypothermic/normothermic kidney conditioning before transplantation, paving the way for combining machine perfusion with EVs-based cell therapy for organ conditioning. HIGHLIGHTS: ·UPCs from porcine urine can be used to generate a cell therapy product based on extracellular vesicles (pUPC-EVs). ·pUPC-EVs injection during HMP and NMP decreases cell damage markers and has an immunomodulatory effect. ·pUPC-EVs-treated kidneys have distinct biochemical, metabolic, and transcriptomic profiles highlighting targets of interest. ·Our results pave the way for combining machine perfusion with EV-based cell therapy for kidney conditioning.

Since wound healing is one of the most important medical challenges and common dressings have not been able to manage this challenge well today, efforts have been increased to achieve an advanced dressing. Mesenchymal stem cells and exosomes derived from them have shown high potential in healing and regenerating wounds due to their immunomodulatory, anti-inflammatory, immunosuppressive, and high regenerative capacities. However, challenges such as the short life of these cells, the low durability of these cells in the wound area, and the low stability of exosomes derived from them have resulted in limitations in their use for wound healing. Nowadays, different scaffolds are considered suitable biomaterials for wound healing. These scaffolds are made of natural or synthetic polymers and have shown promising potential for an ideal dressing that does not have the disadvantages of common dressings. One of the strategies that has attracted much attention today is using these scaffolds for seeding and delivering MSCs and their exosomes. This combined strategy has shown a high potential in enhancing the shelf life of cells and increasing the stability of exosomes. In this review, the combination of different scaffolds with different MSCs or their exosomes for wound healing has been comprehensively discussed.

The therapeutic effect of mesenchymal stem cells (MSCs) in liver cirrhosis is limited by their entrapment in the pulmonary vessels. Thus, the use of MSC-derived exosomes has become a promising strategy. The current work aimed to compare the role of human umbilical cord blood-MSCs (hUCB-MSCs) and their derived exosomes in the alleviation of liver cirrhosis focusing on the role of miR-23b and miR-221 and their direct effectors in inflammatory and autophagic pathways.

Rats were divided into six groups normal controls (negative control), liver cirrhosis group (positive control), liver cirrhotic rats that received conditioned media, liver cirrhotic rats that received hUCB-MSCs, cirrhotic rats that received exosomes, and cirrhotic rats that received both hUCB-MSCs and exosomes. The messenger RNA expression of transforming growth factor-β (TGF-β), Matrix metalloproteinase 9 (MMP 9), fibronectin, collagen type-1 (col1), alpha-smooth muscle actin (α-SMA), Suppressor of Mothers Against Decapentaplegic (SMAD) 2 and 7, Beclin, P62, and light chain 3 (LC3) were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed.

The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated miRNA-221, fibronectin, collagen I, α-SMA, Smad2 (P<0.001, for each), and P62 (P=0.032, P<0.001, P<0.001, respectively). Additionally, the treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly upregulated mTOR, Beclin, LC3, and Smad7 (P<0.001, for each) and miRNA-23 (P=0.021, P<0.001, P<0.001, respectively).

hUCB-MSCs and their derived exosomes ameliorated liver cirrhosis by anti-inflammatory and anti-fibrotic effects besides modulation of autophagy. The exosomes had a better improvement effect either alone or combined with hUCB-MSCs, as proved by improvement in liver function tests, and molecular, histopathological, and immunohistochemical profiles.

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.

Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients.

An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED.

Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications.

MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED.

The arena of exosomal research presents substantial emerging prospects for clinical dermatology applications. This investigation conducts a thorough analysis of the contemporary global research landscape regarding exosomes and their implications for dermatological applications over the preceding decade. Employing bibliometric methodologies, this study meticulously dissects the knowledge framework and identifies dynamic trends within this specialized field. Contemporary scholarly literature spanning the last decade was sourced from the Web of Science Core Collection (WoSCC) database. Subsequent to retrieval, both quantitative and visual analyses of the pertinent publications were performed utilizing the analytical software tools VOSviewer and Citespace. A comprehensive retrieval yielded 545 scholarly articles dated from January 1, 2014, to December 31, 2023. Leading the research forefront are institutions such as Shanghai Jiao Tong University, The Fourth Military Medical University, and Sun Yat-sen University. The most prolific contributors on a national scale are China, the United States, and South Korea. Among the authors, Zhang Bin, Zhang Wei, and Zhang Yan emerge as the most published, with Zhang Bin also achieving the distinction of being the most cited. The International Journal of Molecular Sciences leads in article publications, whereas Stem Cell Research & Therapy holds the pinnacle in citation rankings. Theranostics boasts the highest impact factor among the periodicals. Current research hotspots in this area include Adipose mesenchymal stem cell-derived exosomes(ADSC-Exos), diabetic skin wounds, cutaneous angiogenesis, and the combination of biomaterials and exosomes. This manuscript constitutes the inaugural comprehensive bibliometric analysis that delineates the prevailing research trends and advancements in the clinical application of exosomes in dermatology. These analyses illuminate the contemporary research focal points and trajectories, providing invaluable insights that will inform further exploration within this domain.

Microneedles have recently emerged as a groundbreaking technology in the field of biomedical detection. Notable for their small size and ability to penetrate the superficial layers of the skin, microneedles provide an innovative platform for localized and real-time detection. This review explores the integration of various detection methods with microneedle technology, focusing particularly on its applications in biomedical contexts. First, the common detection methods, such as colorimetric, electrochemical, spectrometric, and fluorescence methods, combined with microneedle technology, are summarized. Then we showcase exemplary uses of microneedle technology in biomedical detection, including the monitoring of blood glucose levels, evaluating infection statuses in skin wounds, facilitating point-of-care testing, and identifying biomarkers in the interstitial fluid of the skin. Microneedle-based detection, with its painless, minimally invasive, and biocompatible approach, holds significant promise for enhancing biological assays. Finally, the review concludes by assessing the future potential and challenges of microneedle detection technology, underscoring its transformative capacity to advance personalized medicine and revolutionize healthcare practices.

Aortic dissection (AD) is a devastating disease with a high mortality rate. Exosomes derived from mesenchymal stem cells (exo-MSCs) offer a promising strategy to restore aortic medial degeneration and combat ferroptosis in AD. However, their rapid degradation in the circulatory system and low treatment efficiency limit their clinical application. Methylacrylated gelatin (Gelma) was reported as a matrix material to achieve controlled release of exosomes. Herein, exo-MSCs-embedded in Gelma hydrogels (Gelma-exos) using ultraviolet light and three-dimensional (3D) printing technology. These Gelma-exos provide a sustained release of exo-MSCs as Gelma gradually degrades, helping to restore aortic medial degeneration and prevent ferroptosis. The sustained release of exosomes can inhibit the phenotypic switch of vascular smooth muscle cells (VSMCs) to a proliferative state, and curb their proliferation and migration. Additionally, the 3D-printed Gelma-exos demonstrated the ability to inhibit ferroptosis in vitro, in vivo and ex vivo experiments. In conclusion, our Gelma-exos, combined with 3D-printed technology, offer an alternative treatment approach for repairing aortic medial degeneration and ferroptosis in AD, potentially reducing the incidence of aortic dissection rupture.

Advancements in understanding skin aging mechanisms, which encompass both external and internal aging processes, have spurred the development of innovative treatments primarily aimed at improving cosmetic appearance. These findings offer the potential for the development of novel therapeutic strategies aimed at achieving long-term, non-therapy-dependent clinical benefits, including the reversal of aging and the mitigation of associated health conditions. Realizing this goal requires further research to establish the safety and efficacy of targeting aging-related skin changes, such as pigmentation, wrinkling, and collagen loss. Systematic investigation is needed to identify the most effective interventions and determine optimal anti-aging treatment strategies. These reviews highlight the features and possible mechanisms of skin aging, as well as the latest progress and future direction of skin aging research, to provide a theoretical basis for new practical anti-skin aging strategies.

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.

The effectiveness and safety of mesenchymal stem cell (MSC) therapy have been substantiated across various diseases. Nevertheless, challenges such as the restricted in vitro expansion capacity of tissue-derived MSCs and the clinical instability due to the high heterogeneity of isolated cells require urgent resolution. The induced pluripotent stem cell-derived MSCs (iPSC-MSCs), which is differentiated from iPSCs via specific experimental pathways, holds considerable potential as a substitute for tissue derived MSCs. Multiple studies have demonstrated that iPSCs can be differentiated into iPSC-MSCs through diverse differentiation strategies. Research suggests that iPSC-MSCs, when compared to tissue derived MSCs, exhibit superior characteristics in terms of proliferation ability, immune modulation capacity, and biological efficiency. In this review, we meticulously described and summarized the experimental methods of iPSC differentiation into iPSC-MSCs, the application of iPSC-MSCs in various disease models, the latest advancements in clinically relevant iPSC-derived cell products, and the development strategies for the next generation of iPSC-derived therapy products (not only cell products but also their derivatives).

Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.

Diabetes represents a widely acknowledged global public health concern. Diabetic foot ulcer (DFU) stands as one of the most severe complications of diabetes, its occurrence imposing a substantial economic burden on patients, profoundly impacting their quality of life. Despite the deepening comprehension regarding the pathophysiology and cellular as well as molecular responses of DFU, the current therapeutic arsenal falls short of efficacy, failing to offer a comprehensive remedy for deep-seated chronic wounds and microvascular occlusions. Conventional treatments merely afford symptomatic alleviation or retard the disease's advancement, devoid of the capacity to effectuate further restitution of compromised vasculature and nerves. An escalating body of research underscores the prominence of mesenchymal stem cells (MSCs) owing to their paracrine attributes and anti-inflammatory prowess, rendering them a focal point in the realm of chronic wound healing. Presently, MSCs have been validated as a highly promising cellular therapeutic approach for DFU, capable of effectuating cellular repair, epithelialization, granulation tissue formation, and neovascularization by means of targeted differentiation, angiogenesis promotion, immunomodulation, and paracrine activities, thereby fostering wound healing. The secretome of MSCs comprises cytokines, growth factors, chemokines, alongside exosomes harboring mRNA, proteins, and microRNAs, possessing immunomodulatory and regenerative properties. The present study provides a systematic exposition on the etiology of DFU and elucidates the intricate molecular mechanisms and diverse functionalities of MSCs in the context of DFU treatment, thereby furnishing pioneering perspectives aimed at harnessing the therapeutic potential of MSCs for DFU management and advancing wound healing processes.

Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, new methods in regenerative medicine are continually sought, and existing ones are being improved. Small extracellular vesicles (sEVs) have gained attention for their regenerative potential, as evidenced by existing studies conducted by independent research groups. Of particular interest are sEVs derived from the oral mucosa, a tissue renowned for its rapid regeneration and minimal scarring. While the individual regenerative potential of both sEVs and the oral mucosa is somewhat understood, the combined potential of sEVs derived from the oral mucosa has not been sufficiently explored and highlighted in the existing literature. Serving as a broad compendium, it aims to provide scientists with essential and detailed information on this subject, including the nature of the materials employed, isolation and analysis methodologies, and clinical applications. The content of this survey aims to facilitate the comparison of diverse methods for working with sEVs derived from the oral mucosa, aiding in the planning of research endeavors and identifying potential research gaps.