Promote Tissue Repair Research Articles

Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization

Loss of antimicrobial proteins such as REG3 family members compromises the integrity of the intestinal barrier. Here, we demonstrate that overproduction of REG3 proteins can also be detrimental by reducing a protective species in the microbiota. Patients with inflammatory bowel disease (IBD) experiencing flaresdisplayed heightened levels of secreted REG3 proteins that mediated depletion of Enterococcus faecium (Efm) from the gut microbiota. Efm inoculation of mice ameliorated intestinal inflammation through activation of the innate immune receptor NOD2, which was associated with the bacterial DL-endopeptidase SagA that generates NOD2-stimulating muropeptides. NOD2 activation in myeloid cells induced interleukin-1β (IL-1β) secretion to increase the proportion of IL-22-producing CD4+ T helper cells and innate lymphoid cells that promote tissue repair. Finally, Efm was unable to protect mice carrying a NOD2 gene variant commonly found in IBD patients. Our findings demonstrate that inflammation self-perpetuates by causing aberrant antimicrobial activity that disrupts symbiotic relationships with gut microbes.

Triazolothiadiazine derivative positively modulates CXCR4 signaling and improves diabetic wound healing

Development of specific therapies that target and accelerate diabetic wound repair is an urgent need to alleviate pain and suffering and the huge socioeconomic burden of this debilitating disease. C-X-C Motif Chemokine Ligand 12 (CXCL12) also know an stromal cell-derived factor 1α (SDF-1α) is a chemokine that binds the CXC chemokine receptor type 4 (CXCR4) and activates downstream signaling resulting in recruitment of hematopoietic cells to locations of tissue injury and promotes tissue repair. In diabetes, low expression of CXCL12 correlates with impaired wound healing. Activation of CXCR4 receptor signaling with agonists or positive allosteric modulators (PAMs) provides a potential for small molecule therapeutic discovery and development. We recently reported high throughput screening and identification of the CXCR4 partial agonist UCUF-728, characterization of in vitro activity and reduced wound closure time in diabetic mice at 100 μM as a proof-of-concept study. We report here, the discovery of a second chemical scaffold demonstrating increased agonist potency and represented by thiadiazine derivative, UCUF-965. UCUF-965 is a potent partial agonist of β-arrestin recruitment in CXCR4 receptor overexpressing cell line. Furthermore, UCUF-965 potentiates the CXCL12 maximal response in cAMP signaling pathway, activates CXCL12 stimulated migration in lymphoblast cells and modulates the levels of specific microRNA involved in the complex wound repair process, specifically in mouse fibroblasts. Our results indicate that UCUF-965 acts as a PAM agonist of the CXCR4 receptor. Furthermore, UCUF-965 enhanced angiogenesis markers and reduced wound healing time by 36% at 10.0 μM in diabetic mice models compared to untreated control.

Mesenchymal stem cell-neural progenitors are enriched in cell signaling molecules implicated in their therapeutic effect in multiple sclerosis.

Mesenchymal stem cell-neural progenitors (MSC-NP) are a neural derivative of MSCs that are being investigated in clinical trials as an autologous intrathecal cell therapy to treat patients with secondary progressive (SP) or primary progressive (PP) multiple sclerosis (MS). MSC-NPs promote tissue repair through paracrine mechanisms, however which secreted factors mediate the therapeutic potential of MSC-NPs and how this cell population differs from MSCs remain poorly understood. The objective of this study was to define the transcriptional profile of MSCs and MSC-NPs from MS and non-MS donors to better characterize each cell population. MSCs derived from SPMS, PPMS, or non-MS bone marrow donors demonstrated minimal differential gene expression, despite differences in disease status. MSC-NPs from both MS and non-MS-donors exhibited significant differential gene expression compared to MSCs, with 2,156 and 1,467 genes upregulated and downregulated, respectively. Gene ontology analysis demonstrated pronounced downregulation of cell cycle genes in MSC-NPs compared to MSC consistent with reduced proliferation of MSC-NPs in vitro. In addition, MSC-NPs demonstrated significant enrichment of genes involved in cell signaling, cell communication, neuronal differentiation, chemotaxis, migration, and complement activation. These findings suggest that increased cell signaling and chemotactic capability of MSC-NPs may support their therapeutic potential in MS.

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.

Abstract P1072: Microneedle Patch Loaded With Il-4 Macroparticles Facilitates Heart Repair Through Macrophages Mediated Cardiomyocyte Phenotype Transition

Ischemic heart disease remains the leading cause of mortality worldwide, but significant progress has been made in optimizing the treatment of acute myocardial infarction (MI) with percutaneous coronary intervention techniques. However, the increased pool of post-MI survivors has led to a higher prevalence of heart failure (HF) secondary to coronary artery disease, making it a major public health issue. Monocytes recruited from circulation differentiate into pro-inflammatory macrophages (M1-like) responsible for post-MI inflammation and cellular debris removal. As a unique Th2 cell cytokine, Interleukin 4 (IL-4) has been widely established as a powerful agent for the polarization of anti-inflammatory macrophages that promote tissue repair. However, there are limitations such as local and targeted delivery have hampered the successful translation of IL-4 therapy. In this study, we created an IL-4 microparticle-loaded microneedle patch (IL-4 MP-MN) for localized delivery of IL-4 to the MI region and tested the therapeutic effects in a rat model of MI. Our preliminary data suggested that IL-4 MP-MN treatment promoted cardiomyocyte proliferation and induced an anti-inflammatory microenvironment, which further led to a cardiomyocyte phenotype shift from "self-rescue" to "assisted-rescue" mode. Additionally, we successfully translated the therapeutic effects of IL-4 MP-MN in a porcine model of MI for testing therapeutic feasibility, safety, and efficacy.

Inflammation Resolution in the Cardiovascular System: Arterial Hypertension, Atherosclerosis, and Ischemic Heart Disease.

Significance: Chronic inflammation has emerged as a major underlying cause of many prevalent conditions in the Western world, including cardiovascular diseases. Although targeting inflammation has emerged as a promising avenue by which to treat cardiovascular disease, it is also associated with increased risk of infection. Recent Advances: Though previously assumed to be passive, resolution has now been identified as an active process, mediated by unique immunoresolving mediators and mechanisms designed to terminate acute inflammation and promote tissue repair. Recent work has determined that failures of resolution contribute to chronic inflammation and the progression of human disease. Specifically, failure to produce pro-resolving mediators and the impaired clearance of dead cells from inflamed tissue have been identified as major mechanisms by which resolution fails in disease. Critical Issues: Drawing from a rapidly expanding body of experimental and clinical studies, we review here what is known about the role of inflammation resolution in arterial hypertension, atherosclerosis, myocardial infarction, and ischemic heart disease. For each, we discuss the involvement of specialized pro-resolving mediators and pro-reparative cell types, including T regulatory cells, myeloid-derived suppressor cells, and macrophages. Future Directions: Pro-resolving therapies offer the promise of limiting chronic inflammation without impairing host defense. Therefore, it is imperative to better understand the mechanisms underlying resolution to identify therapeutic targets. Antioxid. Redox Signal. 40, 292-316.

MSC-Derived Exosomes Ameliorate Intervertebral Disc Degeneration By Regulating the Keap1/Nrf2 Axis.

Bone marrow mesenchymal stem cell derived exosomes (BMSC-exos) are a crucial means of intercellular communication and can regulate a range of biological processes by reducing inflammation, decreasing apoptosis and promoting tissue repair. The process of intervertebral disc degeneration (IVDD) is accompanied by increased reactive oxygen species (ROS) because of a decrease in the expression of Nrf2, a critical transcription factor that resists excessive ROS. Our study demonstrated that BMSC-exos decreased ROS production by inhibiting Keap1 and promoting Nrf2 expression, attenuating the apoptosis, inflammation, and degeneration of nucelus pulposus (NP) cells. BMSC-exos promoted an increase in Nrf2 and nuclear translocation, while NF-κB expression was downregulated during this process. Additionally, the expression of antioxidative proteins was elevated after treatment with BMSC-exos. In vivo, we found more NP tissue retention in the BMSC-exos-treated group, along with more expression of Nrf2 and antioxidant-related proteins. Our findings demonstrated for the first time that BMSC-exos could restore the down-regulated antioxidant response system in degenerating NP cells by modulating the Keap1/Nrf2 axis. BMSC-exos could be used as an immediate ROS modulator in the treatment of intervertebral disc degeneration. When BMSC-exos were uptaken by NPCs, the expression of Keap1 decreased and this led to increased expression of Nrf2. Nuclear translocation of Nrf2 then promoted the synthesis of antioxidants against ROS and inhibited NF-kB signalling. Cellular inflammation, apoptosis, and ECM-related indicators were further reduced. Together, the process of IVDD was alleviated.

Lymphatic Regulation in Tissue Repair and Regeneration: Recent Advances and Future Perspective.

Lymphatic vasculature plays essential role in interstitial tissue uptake, immune cell transport and dietary lipid absorption. Increasing evidence has demonstrated the contribution of lymphangiogenesis to tissue repair and regeneration, which is associated with multiple factors such as improved tissue homeostasis, inflammation resolution, and immunomodulation effects. Meanwhile, lymphangiogenesis has the potential to regulate cell growth and proliferation through paracrine effects. Lymphatic vessels can also be important components of the stem cell niche and participate in regulating stem cell quiescency or activity. In perspective, the functions and mechanisms of lymphatic vessels in tissue repair and regeneration deserve further investigation. Novel strategies to stimulate lymphangiogenesis by using pharmacological, genetic, and lymphatic tissue engineering will be prospective to promote tissue repair and regeneration.

Metabolic reprogramming of proinflammatory macrophages by target delivered roburic acid effectively ameliorates rheumatoid arthritis symptoms

Rheumatoid arthritis (RA) is a common chronic inflammatory disorder that usually affects joints. It was found that roburic acid (RBA), an ingredient from anti-RA herb Gentiana macrophylla Pall., displayed strong anti-inflammatory activity. However, its medical application is limited by its hydrophobicity, lack of targeting capability and unclear functional mechanism. Here, we constructed a pH responsive dual-target drug delivery system hitchhiking RBA (RBA-NPs) that targeted both CD44 and folate receptors, and investigated its pharmacological mechanism. In rat RA model, the nanocarriers effectively delivered RBA to inflammatory sites and significantly enhanced the therapeutic outcomes compared with free RBA, as well as strongly reducing inflammatory cytokine levels and promoting tissue repair. Following analysis revealed that M1 macrophages in the joints were reprogrammed to M2 phenotype by RBA. Since the balance of pro- and anti-inflammatory macrophages play important roles in maintaining immune homeostasis and preventing excessive inflammation in RA, this reprogramming is likely responsible for the anti-RA effect. Furthermore, we revealed that RBA-NPs drove M1-to-M2 phenotypic switch by down-regulating the glycolysis level via blocking ERK/HIF-1α/GLUT1 pathway. Thus, our work not only developed a targeting delivery system that remarkably improved the anti-RA efficiency of RBA, but also identified a potential molecular target to reversely reprogram macrophages though energy metabolism regulation.

Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice.

Endometriosis is a chronic inflammatory gynecological disorder regulated by estrogen and characterized by the growth of endometrial tissue outside the uterus. We have previously demonstrated that mesenchymal stem cells (MSCs) contribute directly to endometriosis. Here, we investigated an indirect effect; we hypothesized that MSCs may also impact the bone marrow (BM) by regulating bone marrow-derived inflammatory cells. Endometriosis was induced in mice by transplanting uterine tissue into recipient mice followed by BM transplant. Control or MSC conditioned BM was injected retro-orbitally. Direct administration of MSCs outside of the setting of BM conditioning did not alter endometriosis. Coculture of an undifferentiated macrophage cell line with MSCs in vitro led to a reduction of M1 and increased M2 macrophages as determined by fluorescence-activated cell sorting and western blot. Conditioning of BM with MSCs and transplantation into a mouse model inhibited endometriotic lesion development and reduced lesion volume by sevenfold compared to BM transplant without MSCs conditioning. Immunohistochemistry and immunofluorescence showed that MSC conditioned BM reduced the infiltration of macrophages and neutrophils into endometriotic lesions by twofold and decreased the proportion of M1 compared to M2 macrophages, reducing inflammation and likely promoting tissue repair. Expression of several inflammatory markers measured by quantitative real-time polymerase chain reaction, including tumor necrosis factor alpha and CXCR4, was decreased in the conditioned BM. Donor MSCs were not detected in recipient BM or endometriotic lesions, suggesting that MSCs actively program the transplanted BM. Taken together, these data show that individual characteristics of BM have an unexpected role in the development of endometriosis. BM remodeling and alterations in the inflammatory response are also potential treatments for endometriosis. Identification of the molecular basis for BM programing by MSCs will lead to a better understanding of the immune system contribution to this disease and may lead to new therapeutic targets for endometriosis.

Preemptive transcranial direct current stimulation induces analgesia, prevents chronic inflammation and fibrosis, and promotes tissue repair in a rat model of postoperative pain

This study evaluated the effects of previous exposure to Transcranial Direct Current Stimulation (tDCS) on nociceptive, neuroinflammatory, and neurochemical parameters, in rats subjected to an incisional pain model. Forty adult male Wistar rats (60 days old; weighing ∼ 250 g) were divided into five groups: 1. control (C); 2. drugs (D); 3. surgery (S); 4. surgery + sham-tDCS (SsT) and 5. surgery + tDCS (ST). Bimodal tDCS (0.5 mA) was applied for 20 min/day/8 days before the incisional model. Mechanical allodynia (von Frey) was evaluated at different time points after surgery. Cytokines and BDNF levels were evaluated in the cerebral cortex, hippocampus, brainstem, and spinal cord. Histology and activity of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) were evaluated in the surgical lesion sites in the right hind paw. The results demonstrate that the surgery procedure increased BDNF and IL-6 levels in the spinal cord levels in the hippocampus, and decreased IL-1β and IL-6 levels in the cerebral cortex, IL-6 levels in the hippocampus, and IL-10 levels in the brainstem and hippocampus. In addition, preemptive tDCS was effective in controlling postoperative pain, increasing BDNF, IL-6, and IL-10 levels in the spinal cord and brainstem, increasing IL-1β in the spinal cord, and decreasing IL-6 levels in the cerebral cortex and hippocampus, IL-1β and IL-10 levels in the hippocampus. Preemptive tDCS also contributes to tissue repair, preventing chronic inflammation, and consequent fibrosis. Thus, these findings imply that preemptive methods for postoperative pain management should be considered an interesting pain management strategy, and may contribute to the development of clinical applications for tDCS in surgical situations.

Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival fibroblasts cells.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic β cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.

Stem cells derived exosomes and biomaterials to modulate autophagy and mend broken hearts

Autophagy maintains cellular homeostasis and plays a crucial role in managing pathological conditions including ischemic myocardial injury leading to heart failure (HF). Despite treatments, no intervention can replace lost cardiomyocytes. Stem cell therapy offers potential for post-myocardial infarction repair but struggles with poor cell retention due to immune rejection. In the search for effective therapies, stem cell-derived extracellular vesicles (EVs), especially exosomes, have emerged as promising tools. These tiny bioactive molecule carriers play vital roles in intercellular communication and tissue engineering. They offer numerous therapeutic benefits including modulating immune responses, promoting tissue repair, and boosting angiogenesis. Additionally, biomaterials provide a conducive 3D microenvironment for cell, exosome, and biomolecule delivery, and enhance heart muscle strength, making it a comprehensive cardiac repair strategy. In this regard, the current review delves into the intricate application of extracellular vesicles (EVs) and biomaterials for managing autophagy in the heart muscle during cardiac injury. Central to our investigation is the exploration of how these elements interact within the context of cardiac repair and regeneration. Additionally, this review also casts light on the formidable challenges that plague this field, such as the issues of safety, efficacy, controlled delivery, and acceptance of these therapeutic strategies for effective clinical translation. Addressing these challenges is crucial for unlocking the full therapeutic potential of EV and biomaterial-based therapies and ensuring their successful translation from bench to bedside.

Combining microfluidics and coaxial 3D-bioprinting for the manufacturing of diabetic wound healing dressings

Diabetic foot ulcers (DFUs) are a crucial complication of diabetes, as in a diabetic wound, each step of the physiological healing process is affected. This entails a more easily infectable wound, and delayed tissue regeneration due to the inflammation that occurs, leading to a drastic decrease in the overall patient's quality of life. As a strategy to manage DFUs, skin alternatives and wound dressings are currently receiving a lot of attention as they keep the wound environment “under control”, while providing bioactive compounds that help to manage infection and inflammation and promote tissue repair. This has been made possible thanks to the advent of emerging technologies such as 3D Bioprinting to produce skin resembling constructs or microfluidics (MFs) that allows the manufacture of nanoparticles (NPs) that act as drug carriers, in a prompt and less expensive way.In the present proof-of-concept study, the possibility of combining two novel and appealing techniques in the manufacturing of wound dressings has been demonstrated for first time. The novelty of this work consists in the combination of liposomes (LPs) encapsulating the active pharmaceutical ingredient (API) into a hydrogel that is further printed into a three-dimensional scaffold for wound dressing; to the knowledge of the authors this has never been done before.A grid-shaped scaffold has been produced through the coaxial 3D bioprinting technique which has allowed to combine, in one single filament, two different bioinks. The inner core of the filament is a nanocomposite hydrogel consisting of hydroxyethyl cellulose (HEC) and PEGylated LPs encapsulated with thyme oil (TO) manufactured via MFs for the first time. The outer shell of the filament, instead, is represented by a hybrid hydrogel composed of sodium alginate/cellulose nanocrystals (SA/CNC) and enriched with free TO. This provides a combination of two different release ratios of the API, a bulk release for the first 24 h thanks to the free TO in the shell of the filament and a sustained release for up to 10 days provided from the API inside the LPs. Confocal Microscopy verified the actual presence of the LPs inside the scaffold after printing and evaluation using the zone of inhibition test proved the antibacterial activity of the manufactured scaffolds against both Gram-positive and Gram-negative bacteria.

Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing.

Macrophages play a crucial role in the complete processes of tissue repair and regeneration, and the activation of M2 polarization is an effective approach to provide a pro-regenerative immune microenvironment. Natural extracellular matrix (ECM) has the capability to modulate macrophage activities via its molecular, physical, and mechanical properties. Inspired by this, an ECM-mimetic hydrogel strategy to modulate macrophages via its dynamic structural characteristics and bioactive cell adhesion sites is proposed. The LZM-SC/SS hydrogel is in situ formed through the amidation reaction between lysozyme (LZM), 4-arm-PEG-SC, and 4-arm-PEG-SS, where LZM provides DGR tripeptide for cell adhesion, 4-arm-PEG-SS provides succinyl ester for dynamic hydrolysis, and 4-arm-PEG-SC balances the stability and dynamics of the network. In vitro and subcutaneous tests indicate the dynamic structural evolution and cell adhesion capacity promotes macrophage movement and M2 polarization synergistically. Comprehensive bioinformatic analysis further confirms the immunomodulatory ability, and reveals a significant correlation between M2 polarization and cell adhesion. A full-thickness wound model is employed to validate the induced M2 polarization, vessel development, and accelerated healing by LZM-SC/SS. This study represents a pioneering exploration of macrophage modulation by biomaterials' structures and components rather than drug or cytokines and provides new strategies to promote tissue repair and regeneration.

Antibacterial Thermosensitive Silver-Hydrogel Nanocomposite Improves Wound Healing.

Bacterial infection and poor cell recruitment are among the main factors that prolong wound healing. To address this, a strategy is required that can prevent infection while promoting tissue repair. Here, we have created a silver nanoparticle-based hydrogel composite that is antibacterial and provides nutrients for cell growth, while filling cavities of various geometries in wounds that are difficult to reach with other dressings. Silver nanoparticles (AgNPs) were synthesized by chemical reduction and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and inductively coupled plasma-mass spectroscopy (ICP-MS). Using varying concentrations of AgNPs (200, 400, and 600 ppm), several collagen-based silver-hydrogel nanocomposite candidates were generated. The impact of these candidates on wound healing was assessed in a rat splinted wound model, while their ability to prevent wound infection from a contaminated surface was assessed using a rat subcutaneous infection model. Biocompatibility was assessed using the standard MTT assay and in vivo histological analyses. Synthesized AgNPs were spherical and stable, and while hydrogel alone did not have any antibacterial effect, AgNP-hydrogel composites showed significant antibacterial activity both in vitro and in vivo. Wound healing was found to be accelerated with AgNP-hydrogel composite treatment, and no negative effects were observed compared to the control group. The formulations were non-cytotoxic and did not differ significantly in hematological and biochemical factors from the control group in the in vivo study. By presenting promising antibacterial and wound healing activities, silver-hydrogel nanocomposite offers a safe therapeutic option that can be used as a functional scaffold for an acceleration of wound healing.

Analyzing the Current Umbilical Cord-derived Mesenchymal Stem Cell Secretome Evidence for Erectile Dysfunction Management

Erectile dysfunction (ED) impacts millions of men, especially older men, and current treatment options, including tadalafil, phosphodiesterase type 5 inhibitors, and short-acting testosterone, are ineffective. This necessitates the immediate development of effective alternative ED treatments. In recent years, attention has been drawn to the secretome of umbilical cord-derived mesenchymal stem cells (UC-MSCs) due to its anti-inflammatory and immunomodulatory properties, which can reduce inflammation and promote tissue repair. The UC-MSCs secretome contains numerous growth factors, such as vascular endothelial growth factor, insulin-like growth factor 1 (IGF-1), and basic fibroblast growth factor (bFGF), which are essential for promoting endothelial cell proliferation and penile blood flow. This review seeks to examine the existing evidence on the use of stem cells, with a focus on UC-MSCs secretome, as a potential treatment modality for erectile dysfunction (ED). By reviewing the PubMed, Google Scholar, and Scopus databases, a comprehensive narrative review was conducted. Included among the search queries were "erectile dysfunction," "stem cells," "mesenchymal stem cells," "umbilical cord," and "secretome." Only research published in English within the past decade was included in the analysis. The findings indicate that the secretome of UC-MSCs has promise for treating ED. The secretome is composed of growth factors, cytokines, and other bioactive compounds that promote tissue repair and regeneration via paracrine effects on adjacent cells. The administration of UC-MSCs improved erectile function, penile blood flow, and smooth muscle content. In addition, discarded UC-MSCs serve as a cost-effective and copious source of ethically acceptable and immunogenic UC-MSCs with low immunogenicity. The secretome of UC-MSCs offers a potential therapeutic strategy for treating erectile dysfunction. However, further preclinical and clinical research must be done to determine the safety and efficacy of stem cell-based treatments for erectile dysfunction.

A systematic review of the therapeutic effect of platelet-rich plasma for treating traumatic brain injury

Abstract Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and thus a significant public health concern. It can result in a range of physical, cognitive, and emotional impairments, which can significantly impact the quality of life of affected individuals and their families. Despite advances in the management of TBI, no effective treatment fully restores neurological function. Platelet-rich plasma (PRP) is a promising therapeutic approach for the treatment of TBI that has gained increasing attention in recent years. PRP is a blood product containing high concentration of platelets rich in growth factors and other bioactive molecules that can promote tissue repair and regeneration. PRP has been used in various clinical settings to accelerate healing and reduce inflammation, and there is growing evidence that it may have therapeutic benefits for TBI. This study seeks to gather evidence-based information on the therapeutic effect of PRP in the treatment of TBI. This protocol will follow the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis [PRISMA] guideline 2020. In this review, we determined four primary central databases as sources of information: PubMed, EMBASE, SCOPUS, and Cochrane Central Register of Controlled Trails. This Project was registered on the International Prospective Register of Systematic Reviews [PROSPERO]. Ethics and dissemination: Ethical approval for this study was not needed as we used alread y published studies to run this current study. Study findings will be published in journals and presented at conferences for broader dissemination. PROSPERO Registration N°: CRD42023426358.

Mesenchymal stem cells: An efficient celltherapy for tendon repair (Review).

Tendon injury is a common disorder of the musculoskeletal system caused by overuse or trauma. With increasing incidence of tendon injuries, it is necessary to find an effective treatment. Mesenchymal stem cells (MSCs) are attracting attention because of their high proliferative and self‑renewal capacity. These functions of MSCs show promise in treating a variety of diseases, including immune and musculoskeletal system disorder and cardiovascular disease, and show especially satisfactory effects in the treatment of tendon injury. First, since MSCs have multidirectional differentiation potential, they differentiate into specific cells after induction invivo and invitro. Furthermore, MSCs have paracrine functions and can secrete biologically active molecules and exosomes such as cytokines, growth factors and chemokines to promote tissue repair and regeneration. In tendon injury, MSCs promote tendon repair through four mechanisms: Decreasing inflammation and promoting neovascularization and cell proliferation and differentiation. They are also involved in extracellular matrix reorganization by promoting collagen production and transforming typeIII collagen fibers to typeI collagen fibers. The present review summarized preclinical experiments with different sources of MSCs and their mechanisms in tendon repair, as well as the limitations of MSCs in current clinical applications and directions that need to be explored in the future.

An Injectable and Antifouling Supramolecular Polymer Hydrogel with Microenvironment-Regulatory Function to Prevent Peritendinous Adhesion and Promote Tendon Repair.

The imbalance of extrinsic and intrinsic healing of tendon is thought to be the main cause of peritendinous adhesions. In this work, we prepare an injectable supramolecular poly(N-(2-hydroxypropyl) acrylamide) (PHPAm) hydrogel merely via side chain hydrogen-bonding crosslinks. This PHPAm exhibits good antifouling and self-healing properties. The supramolecular hydrogel simultaneously loaded with Prussian blue (PB) nanoparticles and platelet lysate (PL) is exlpored as a functional physical barrier, which could significantly resist the adhesion of fibrin and fibroblasts, attenuate the local inflammatory response, and enhance the tenocytes activity, thus balancing extrinsic and intrinsic healing. The PHPAm hydrogel is shown to prevent peritendinous adhesions considerably by inhibiting NF-κB inflammatory pathway and TGF-β1/Smad3-mediated fibrosis pathway, thereby significantly improving tendon repair by releasing bioactive factors to regulate the tenocytes behavior. This work provides a new strategy for developing physical barriers to prevent peritendinous adhesions and promote tissue repair effectively. This article is protected by copyright. All rights reserved.