Age-related macular degeneration (AMD) is a debilitating retinal disorder that may lead to progressive vision loss. One contributing factor to AMD pathogenesis is excessive blue light (BL) exposure. In this study, we investigated the therapeutic potential of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSC-EXs) in addressing BL-induced damage to ARPE-19 human retinal pigment epithelial (RPE) cells and explored the underlying mechanisms. Our findings revealed that BL exposure induced morphological alterations in ARPE-19 cells, accompanied by a time-dependent decline in cell viability, increased apoptosis, heightened oxidative stress, and inflammatory responses; however, hUCMSC-EXs dose-dependently mitigated BL-induced ARPE-19 cell damage. Interestingly, hUCMSC-EXs were found to suppress the upregulation of fibroblast growth factor 2 (FGF2) in BL-exposed ARPE-19 cells. Furthermore, FGF2 overexpression partially counteracted the inhibitory effects of hUCMSC-EXs on FGF2 expression and compromised the protective benefits of hUCMSC-EXs against BL-induced ARPE-19 cell damage. In conclusion, our results suggest that hUCMSC-EXs shield ARPE-19 cells from BL-induced harm by inhibiting FGF2 expression.

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.

This narrative review focuses on innovative treatment approaches to diabetic retinopathy to meet the urgent demand for advancements in managing both the early and late stages of the disease. Recent studies highlight the potential of adipose stem cells and their secreted factors in mitigating the retinal complications of diabetes, with promising results in improving visual acuity and reducing inflammation and angiogenesis in diabetic retinopathy. However, caution is warranted regarding the safety and long-term therapeutic effects of adipose stem cells transplantation. Bone marrow mesenchymal stem cells can also mitigate retinal damage in diabetic retinopathy. Studies demonstrate that bone marrow mesenchymal stem cells-derived exosomes can suppress the Wnt/β-catenin pathway, reducing oxidative stress, inflammation, and angiogenesis in the diabetic retina, offering promise for future diabetic retinopathy treatments. Nanotechnology has the ability to precisely target the retina and minimize systemic side effects. Nanoparticles and nanocarriers offer improved bioavailability, sustained release of therapeutics, and potential for synergistic effects. They can be a new way of effective treatment and prevention of diabetic retinopathy. Activation and modulation of PPARα as a means for diabetic retinopathy treatment has been widely investigated in recent years and demonstrated promising effects in clinical trials. PPARα activation turned out to be a promising therapeutic method for treating dyslipidemia, inflammation, and insulin sensitivity. The combination of PPARα modulators with small molecules offers an interesting perspective for retinal diseases' therapy.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration. Recent studies have delved into the molecular mechanisms underlying MSC-EV-mediated therapeutic effects. Exosomal microRNAs (miRNAs) have been identified as key regulators of various cellular processes involved in SCI pathogenesis and repair. These miRNAs can influence inflammation, oxidative stress, and apoptosis by modulating gene expression. This review summarized the current state of MSC-EV-based therapies for SCI, highlighting the underlying mechanisms and potential clinical applications. We discussed the challenges and limitations of translating these therapies into clinical practice, such as inconsistent EV production, complex cargo composition, and the need for targeted delivery strategies. Future research should focus on optimizing EV production and characterization, identifying key therapeutic miRNAs, and developing innovative delivery systems to maximize the therapeutic potential of MSC-EVs in SCI.

Parkinson's disease (PD) is a progressive neurodegenerative disorder with symptoms including tremor and bradykinesia, while traditional dopamine replacement therapy and hypothalamic deep brain stimulation can temporarily relieve patients' symptoms, they cannot cure the disease. Hence, discovering new methods is crucial to designing more effective therapeutic approaches to address the condition. In our previous study, we found that exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hucMSCs) repaired a PD model by inducing dopaminergic neuron autophagy and inhibiting microglia. However, it is not clear whether its therapeutic effect is related to inhibiting apoptosis by inhibiting caspase-3 expression.

Three intervention schemes were used concerning previous literature, and the dosage of each scheme is the same, with different dosing intervals and treatment courses and to compare the aspects of behavior, histomorphology, and biochemical indexes. To predict and determine target gene enrichment, high-throughput sequencing and miRNA expression profiling of exosomes, GO and KEGG analysis, and Western blot were used.

Exos labeled with PKH67 were found to reach the substantia nigra through the bloodbrain barrier and existed in the liver and spleen. 6-hydroxydopamine (6-OHDA) induced PD rats were treated with Exos every two days for one month, which alleviated the asymmetric rotation induced by morphine, reduced the loss of dopaminergic neurons in the substantia nigra, and increased dopamine levels in the striatum. The effect became more significant as the treatment time was extended to two months. These results suggest that hucMSCs-Exos can inhibit the 6-OHDA- induced neuron damage in PD rats, and its neuroprotective effects may be mediated by inhibiting cell apoptosis. Through high-throughput sequencing of miRNA, potential targets for Exos to inhibit apoptosis may be BAD, IKBKB, TRAF2, BCL2, and CYCS.

The above results indicate that hucMSCs-Exos can inhibit 6-OHDA-induced damage in PD rats, and its neuroprotective effect may be mediated by inhibiting cell apoptosis.

Patients with steatotic liver disease may show mild cognitive impairment. Rats with mild liver damage reproduce this cognitive impairment, which is mediated by neuroinflammation that alters glutamate neurotransmission in the hippocampus. Treatment with extracellular vesicles (EV) from mesenchymal stem cells (MSC) reduces neuroinflammation and improves cognitive impairment in different animal models of neurological diseases. TGFβ in these EVs seems to be involved in its beneficial effects. The aim of this work was to assess if MSCs-EVs may improve cognitive impairment in rats with mild liver damage and to analyze the underlying mechanisms, assessing the effects on hippocampal neuroinflammation and neurotransmission. We also aimed to analyze the role of TGFβ in the in vivo effects of MSCs-EVs.

Male Wistar rats with CCl4-induced mild liver damage were treated with EVs from unmodified MSC or with EVs derived from TGFβ-silenced MSCs and its effects on cognitive function and on neuroinflammation and altered neurotransmission in the hippocampus were analysed.

Unmodified MSC-EVs reversed microglia activation and TNFα content, restoring membrane expression of NR2 subunit of NMDA receptor and improved object location memory. In contrast, EVs derived from TGFβ-silenced MSCs did not induce these effects but reversed astrocyte activation, IL-1β content and altered GluA2 AMPA receptor subunit membrane expression leading to improvement of learning and working memory in the radial maze.

EVs from MSCs with TGFβ silenced induce different effects on behavior, neuroinflammation and neurotransmitter receptors alterations than unmodified MSC-EVs, indicating that the modification of TGFβ in the MSC-EVs has a notable effect on the consequences of the treatment. This work shows that treatment with MSC-EVs improves learning and memory in a model of mild liver damage and MHE in rats, suggesting that MSC-EVs may be a good therapeutic option to reverse cognitive impairment in patients with steatotic liver disease.

Inflammation and autoimmune diseases (AD) are common outcomes of an overactive immune system. Inflammation occurs due to the immune system reacting to damaging stimuli. Exosomes are being recognized as an advanced therapeutic approach for addressing an overactive immune system, positioning them as a promising option for treating AD. Mesenchymal stem cells (MSCs) release exosomes that have strong immunomodulatory effects, influenced by their cell of origin. MSCs-exosomes, being a cell-free therapy, exhibit less toxicity and provoke a diminished immune response compared to cell-based therapies. Exosomal non-coding RNAs (ncRNA), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are intricately linked to various biological and functional aspects of human health. Exosomal ncRNAs can lead to tissue malfunction, aging, and illnesses when they experience tissue-specific alterations as a result of various internal or external problems. In this study, we will examine current trends in exosomal ncRNA researches regarding AD. Then, therapeutic uses of MSCs-exosomal ncRNA will be outlined, with a particle focus on the underlying molecular mechanisms.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system. Recent research has revealed that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), containing specific miRNAs, possess immunomodulatory properties and have demonstrated therapeutic potential in the treatment of MS. This study aimed to investigate the role MSC-EVs, containing microRNA-181a-5p (miR-181a-5p) in both experimental autoimmune encephalomyelitis (EAE), an established animal model of MS, and lipopolysaccharide-stimulated BV2 microglia. We evaluated clinical symptoms and inflammatory responses in EAE mice following intrathecal injections of MSC-EVs. MSC-EVs containing miR-181a-5p were co-cultured with microglia to explore their impact on inflammation and cell pyroptosis. We validated the interaction between miR-181a-5p and its downstream regulators and conducted in vivo verification by injecting manipulated EVs containing miR-181a-5p into EAE mice. Our results demonstrated that MSC-EVs, containing miR-181a-5p reduced the clinical symptoms of EAE mice. Furthermore, we observed downregulation of miR-181a-5p in EAE model mice, and its expression was restored after treatment with MSC-EVs, which corresponded to suppressed microglial inflammation and pyroptosis. Additionally, EVs containing miR-181a-5p mitigated spinal cord injury and demyelination in EAE mice. Mechanistically, ubiquitin-specific protease 15 (USP15) exhibited high expression in EAE mice, and miR-181a-5p was specifically targeted and bound to USP15, thereby regulating the RelA/NEK7 axis. In conclusion, MSC-EVs containing miR-181a-5p inhibit microglial inflammation and pyroptosis through the USP15-mediated RelA/NEK7 axis, thus alleviating the clinical symptoms of EAE. These findings present a potential therapeutic approach for the treatment of MS.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

The blood-retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A2 activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs. The data obtained highlighted the potential of autologous differentiated ASCs in future clinical applications based on cell therapy to counteract the damage induced by DR.

Brain remodeling after an ischemic stroke represents a promising avenue for exploring the cellular mechanisms of endogenous brain repair. A deeper understanding of these mechanisms is crucial for optimizing the safety and efficacy of neuroprotective treatments for stroke patients. Here, we interrogated the role of extracellular vesicles, particularly exosomes, as potential mediators of endogenous repair within the neurovascular unit (NVU). We hypothesized that these extracellular vesicles may play a role in achieving transient stroke neuroprotection. Using the established ischemic stroke model of middle cerebral artery occlusion in adult rats, we detected a surged in the extracellular vesicle marker CD63 in the peri-infarct area that either juxtaposed or co-localized with GFAP-positive glial cells, MAP2-labeled young neurons, and VEGF-marked angiogenic cells. This novel observation that CD63 exosomes spatially and temporally approximated glial activation, neurogenesis, and angiogenesis suggests that extracellular vesicles, especially exosomes, contribute to the endogenous repair of the NVU, warranting exploration of extracellular vesicle-based stroke therapeutics.

With the rapid development of stem cell research in modern times, stem cell-based therapy has opened a new era of tissue regeneration, becoming one of the most promising strategies for currently untreatable retinal diseases. Among the various sources of stem cells, adipose tissue-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic modality due to their characteristics and multiple functions, which include immunoregulation, anti-apoptosis of neurons, cytokine and growth factor secretion, and antioxidative activities. Studies have shown that ADSCs can facilitate the replacement of dying cells, promote tissue remodeling and regeneration, and support the survival and growth of retinal cells. Recent studies in this field have provided numerous experiments using different preclinical models. The aim of our review is to provide an overview of the therapeutic strategies, modern-day clinical trials, experimental models, and potential clinical use of this fascinating class of cells in addressing retinal disorders and diseases.

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.

The most prevalent type of alopecia is androgenetic alopecia (AGA), which has a high prevalence but no effective treatment. Elevated dihydrotestosterone (DHT) level in the balding area was usually thought to be critical in the pathophysiology of AGA. The canonical Wnt/β-catenin signaling pathway plays a key role in promoting hair follicle development and sustaining the hair follicle cycle. Adipose-derived stem cell exosomes (ADSC-Exos) are widely used in the field of regenerative medicine due to the advantages of being cell free and immune privileged. Still, few studies have reported the therapeutic effect on hair disorders. As a result, we sought to understand how ADSC-Exos affected hair growth and explore the possibility that ADSC-Exos could counteract the hair-growth-inhibiting effects of DHT. This research using human hair follicle organs, in vitro dermal papilla cells, and in vivo animal models showed that ADSC-Exos not only encouraged healthy hair growth but also counteracted the inhibitory effects of DHT on hair growth. Additionally, we discovered that ADSC-Exos increased Ser9 phosphorylated glycogen synthase kinase-3β levels and facilitated nuclear translocation of β-catenin, which may have been blocked by the specific Wnt/β-catenin signaling pathway inhibitor dickkopf-related protein 1. Our findings suggested that ADSC-Exos are essential for hair regeneration, which is anticipated to open up new therapeutic possibilities for clinical alopecia, particularly for the treatment of AGA.

Due to their potent immunoregulatory and angio-modulatory properties, mesenchymal stem cells (MSCs) and their exosomes (MSC-Exos) have emerged as potential game-changers in regenerative ophthalmology, particularly for the personalized treatment of inflammatory diseases. MSCs suppress detrimental immune responses in the eyes and alleviate ongoing inflammation in ocular tissues by modulating the phenotype and function of all immune cells that play pathogenic roles in the development and progression of inflammatory eye diseases. MSC-Exos, due to their nano-sized dimension and lipid envelope, easily bypass all barriers in the eyes and deliver MSC-sourced bioactive compounds directly to target cells. Although MSCs and their exosomes offer a novel approach to treating immune cell-driven eye diseases, further research is needed to optimize their therapeutic efficacy. A significant number of experimental studies is currently focused on the delineation of intracellular targets, which crucially contribute to the immunosuppressive and anti-inflammatory effects of MSCs and MSC-Exos. The activation of NLRP3 inflammasome induces programmed cell death of epithelial cells, induces the generation of inflammatory phenotypes in eye-infiltrated immune cells, and enhances the expression of adhesion molecules on ECs facilitating the recruitment of circulating leukocytes in injured and inflamed eyes. In this review article, we summarize current knowledge about signaling pathways that are responsible for NLRP3 inflammasome-driven intraocular inflammation and we emphasize molecular mechanisms that regulate MSC-based modulation of NLRP3-driven signaling in eye-infiltrated immune cells, providing evidence that NLRP3 inflammasome should be considered a potentially new therapeutic target for MSCs and MSC-Exo-based treatment of inflammatory eye diseases.

Because of their unique capacity for differentiation to a diversity of cell lineages and immunosuppressive properties, mesenchymal stem cells (MSC) are being looked at as a potential new treatment option in ophthalmology. The MSCs derived from all tissue sources possess immunomodulatory attributes through cell-to-cell contact and releasing a myriad of immunomodulatory factors (IL-10, TGF-β, growth-related oncogene (GRO), indoleamine 2,3 dioxygenase (IDO), nitric oxide (NO), interleukin 1 receptor antagonist (IL-1Ra), prostaglandin E2 (PGE2)). Such mediators, in turn, alter both the phenotype and action of all immune cells that serve a pathogenic role in the progression of inflammation in eye diseases. Exosomes from MSCs, as natural nano-particles, contain the majority of the bioactive components of parental MSCs and can easily by-pass all biological barriers to reach the target epithelial and immune cells in the eye without interfering with nearby parenchymal cells, thus having no serious side effects. We outlined the most recent research on the molecular mechanisms underlying the therapeutic benefits of MSC and MSC-exosome in the treatment of inflammatory eye diseases in the current article.

In recent years, mesenchymal stem cells (MSC) have been considered the most effective source for regenerative medicine, especially due to released soluble paracrine bioactive components and extracellular vesicles. These factors, collectively called the secretome, play crucial roles in immunomodulation and in improving survival and regeneration capabilities of injured tissue. Recently, there has been a growing interest in the secretome released by retinal cytotypes, especially retinal pigment epithelium and Müller glia cells. The latter trophic factors represent the key to preserving morphofunctional integrity of the retina, regulating biological pathways involved in survival, function and responding to injury. Furthermore, these factors can play a pivotal role in onset and progression of retinal diseases after damage of cell secretory function. In this review, we delineated the importance of cross-talk between MSCs and retinal cells, focusing on common/induced secreted factors, during experimental therapy for retinal diseases. The cross-link between the MSC and retinal cell secretomes suggests that the MSC secretome can modulate the retinal cell secretome and vice versa. For example, the MSC secretome can protect retinal cells from degeneration by reducing oxidative stress, autophagy and programmed cell death. Conversely, the retinal cell secretome can influence the MSC secretome by inducing changes in MSC gene expression and phenotype.

Exosomes are 30-150 nm extracellular vesicles that are secreted by almost all types of cells. Exosomes contain a variety of biologically active substances, such as proteins, nucleic acids, and lipids, and are important in the intercellular communication of biological mediators involved in nerve injury and repair, vascular regeneration, immune response, fibrosis formation, and many other pathophysiological processes. Although it has been extensively studied in the field of cancer, the exploration of ocular diseases has only just begun. Here, we discuss the latest developments in exosomes for age-related macular degeneration (AMD), including the pathogenesis of exosomes in age-related macular degeneration, their potential as diagnostic markers, and therapeutic vectors of the disease. Finally, the study of exosomes in age-related macular degeneration is still relatively few, and more detailed basic research and clinical trials are needed to verify its application in treatment and diagnosis, so as to adopt more personalized diagnosis and treatment strategies to stop the progression of age-related macular degeneration.

Exosomes are membrane-surrounded extracellular vesicles released by almost all cell types, which mediate intercellular communications by delivering bioactive molecules from secretory cells to recipient cells. Long noncoding RNAs (lncRNAs) are a large class of non-(protein)-coding RNAs with lengths exceeding 200 nucleotides that are very active in the development of cardiovascular diseases (CVDs). Increasing evidence suggests that exosomal lncRNAs also play important roles in the progress of CVDs. We focus on the current available studies regarding these extracellular lncRNAs secreted and absorbed by cardiomyocytes and their functional roles in CVDs, hopefully providing a basis for deeper understanding of the pathological mechanisms of CVDs and their potential for clinical diagnosis and therapy.

Stem cells (SCs) have evolved as an interesting and viable factor in ophthalmologic patient care in the past decades. SCs have been classified as either embryonic, mesenchymal, tissue-specific, or induced pluripotent cells. Multiple novel management techniques and clinical trials have been established to date. While available publications are predominantly animal-model-based, significant material is derived from human studies and case-selected scenarios. This possibility of explanting cells from viable tissue to regenerate/repair damaged tissue points to an exciting future of therapeutic options in all fields of medicine, and ophthalmology is surely not left out. Adipose tissue obtained from lipo-aspirates has been shown to produce mesenchymal SCs that are potentially useful in different body parts, including the oculo-visual system. An overview of the anatomy, physiology, and extraction process for adipose-tissue-derived stem cells (ADSC) is important for better understanding the potential therapeutic benefits. This review examines published data on ADSCs in immune-modulatory, therapeutic, and regenerative treatments. We also look at the future of ADSC applications for ophthalmic patient care. The adverse effects of this relatively novel therapy are also discussed.

The role of mesenchymal stem cells (MSCs) in the breast tumor microenvironment (TME) is significant and multifaceted. MSCs are recruited to breast tumor sites through molecular signals released by tumor sites. Once in the TME, MSCs undergo polarization and interact with various cell populations, including immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), and breast cancer cells. In most cases, MSCs play roles in breast cancer therapeutic resistance, but there is also evidence that indicates their abilities to sensitize cancer cells to chemotherapy and radiotherapy. MSCs possess inherent regenerative and homing properties, making them attractive candidates for cell-based therapies. Therefore, MSCs can be engineered to express therapeutic molecules or deliver anti-cancer agents directly to tumor sites. Unraveling the intricate relationship between MSCs and the breast TME has the potential to uncover novel therapeutic targets and advance our understanding of breast cancer biology.

The stromal vascular fraction (SVF) is a heterogeneous population of cells that, interacting with each other, can affect the processes of regeneration, angiogenesis, and immunomodulation. Over the past 20 years, there has been a trend towards an increase in the number of clinical studies on the therapeutic use of SVF. MicroRNAs (miRNAs) are also important regulators of cellular function and they have been shown to be involved in SVF cellular component function. The purpose of this study was to analyze existing clinical studies on the therapeutic use of SVF including the role of miRNAs in the regulation of the function of the cellular component of SVF as an anti-inflammatory, pro-angiogenic and cell differentiation activity.

The search strategy was to use material from the clinicaltrials.gov website, which focused on the key term "Stromal vascular fraction", and the inclusion and exclusion criteria were divided into two stages.

By August 2022, there were 149 registered clinical trials. Most studies belong to either Phase 1-2 (49.37%), Phase 1 (25.32%) or Phase 2 (22.78%). Most of them focused in the fields of traumatology, neurology/neurosurgery, endocrinology, vascular surgery, and immunology. However, only 8 clinical trials had published results. All of clinical trials have similar preparation methods and 8 clinical trials have positive results with no serious adverse effects.

There appears to be a wide potential for the clinical use of SVF without reports of serious side effects. Many preclinical and clinical studies are currently underway on the use of SVF, and their future results will help to further explore their therapeutic potential. Nevertheless, there are not many studies on the role of miRNAs in the SVF microenvironment; however, this topic is very important for further study of the clinical application of SVF, including safety, in various human diseases.

Severe corneal damage leads to complete vision loss, thereby affecting life quality and impinging heavily on the healthcare system. Current clinical approaches to manage corneal wounds suffer from severe drawbacks, thus requiring the development of alternative strategies. Of late, mesenchymal stromal/stem cell (MSC)-derived extracellular vesicles (EVs) have become a promising tool in the ophthalmic field. In the present study, we topically delivered bone-marrow-derived MSC-EVs (BMSC-EVs), embedded in methylcellulose, in a murine model of alkali-burn-induced corneal damage in order to evaluate their role in corneal repair through histological and molecular analyses, with the support of magnetic resonance imaging. Our data show that BMSC-EVs, used for the first time in this specific formulation on the damaged cornea, modulate cell death, inflammation and angiogenetic programs in the injured tissue, thus leading to a faster recovery of corneal damage. These results were confirmed on cadaveric donor-derived human corneal epithelial cells in vitro. Thus, BMSC-EVs modulate corneal repair dynamics and are promising as a new cell-free approach for intervening on burn wounds, especially in the avascularized region of the eye.