Accelerated Wound Healing by Fibroblasts Differentiated from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in a Pressure Ulcer Animal Model.
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ABSTRACT:
SUBMITTER: Yoon D
PROVIDER: S-EPMC6332923 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Angiogenesis, as an endogenous repair mechanism, plays crucial roles in wound healing and tissue regeneration. However, this process is impaired in the elderly due to aging-related vascular endothelial dysfunction. This study was aimed to explore the pro-angiogenic effects of exosomes from human embryonic stem cells (ESC-Exos) in aged mice of pressure-induced ulcer model and the underlying mechanism. METHODS:Pressure ulcer wounds were created on the back of D-galactose-induced aging mice. ESC-Exos were locally applied onto the wound beds, with PBS as control. The effects of ESC-Exos on wound healing were analyzed by measuring wound closure rates, histological and immunofluorescence analyses. Then, the anti-aging effect of ESC-Exos on vascular endothelial cells was tested in an in vitro D-galactose-induced HUVEC senescence model. RESULTS:ESC-Exos could accelerate wound closure and enhance angiogenesis, and the senescence of vascular endothelial cells was significantly ameliorated after ESC-Exos treatment. In vitro, ESC-Exos could rejuvenate the senescence of endothelial cells and recover compromised proliferation, migratory capacity, and tube formation. This recovery was Nrf2-activation-dependent, since cotreatment with Nrf2 inhibitor Brusatol could abolish the rejuvenative effects of ESC-Exos. Further study revealed that miR-200a was highly enriched in ESC-Exos and played a crucial role in ESC-Exos-mediated rejuvenation through downregulating Keap1, which negatively regulates Nrf2 expression. CONCLUSIONS:ESC-Exos ameliorate endothelial senescence by activating Nrf2 and recover aging-related angiogenic dysfunction, thereby accelerating wound healing in aged mice. ESC-Exos might be a natural nano-biomaterial for aging-related diseases therapy.
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Project description:The results of the present study provide new insights into the mechanism through which NPWT promotes DFU wound healing
2024-07-25 | GSE272918 | GEO
Project description:Keloids are benign dermal tumors that form during wound healing in genetically susceptible individuals. The mechanism(s) of keloid formation is unknown and there is no satisfactory treatment. We have reported differences between fibroblasts cultured from normal scars and keloids that include a pattern of glucocorticoid resistance and altered regulation of genes in several signaling pathways associated with fibrosis, including Wnt and IGF/IGF-binding protein 5 (IGFBP5). As previously reported for glucocorticoid resistance, decreased expression of the Wnt inhibitor secreted frizzled-related protein 1 (SFRP1), matrix metalloproteinase 3 (MMP3), and dermatopontin (DPT), and increased expression of IGFBP5 and jagged 1 (JAG1) are seen only in fibroblasts cultured from the keloid nodule. In vivo, decreased expression of SFRP1 and SFRP2 and increased expression of IGFBP5 proteins are observed only in proliferative keloid tissue. There is no consistent difference in the replicative life span of normal and keloid fibroblasts, and the altered response to hydrocortisone (HC) and differential regulation of a subset of genes in standard culture medium are maintained throughout at least 80% of the culture lifetime. Preliminary studies using ChIP-chip analysis, Trichostatin A, and 5-aza-2'-deoxycytidine further support an epigenetically altered program in keloid fibroblasts that includes an altered pattern of DNA methylation and histone acetylation.
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Project description:Damaged skin cannot prevent harmful bacteria from invading tissues, causing infected wounds and even serious tissue damage. Traditional treatments can not only kill pathogenic bacteria, but also suppress the growth of beneficial bacteria, thus destroying the balance of the damaged skin microbial ecosystem. Here, a living bacterial hydrogel scaffold is reported that accelerates infected wound healing through beneficial bacteria secreting antibacterial substances. Lactobacillus reuteri, a common probiotic, is encapsulated in hydrogel microspheres by emulsion polymerization and further immobilized in a hydrogel network by covalent cross-linking of methacrylate-modified hyaluronic acid. Owing to light-initiated crosslinking, the hydrogel dressing can be generated in situ at the wound site. This hydrogel scaffold not only protects bacteria from immune system attack, but also prevents bacteria from escaping into the local environment, thus avoiding potential threats. Both in vitro and in vivo experiments show that it has excellent ability against harmful bacteria and anti-inflammatory capabilities, promoting infected wound closure and new tissue regeneration. This work may open up new avenues for the application of living bacteria in the clinical management of infected wounds.
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Project description:Objective: To develop a venous leg ulcer (VLU) risk stratification system for use in research and clinical practice. Approach: U.S. Wound Registry data were examined retrospectively and assigned an outcome. Bivariate analysis identified significant variables (p < 0.05) that were used to create a multivariable logistic regression model. Ulcers with data for wound area at the first visit before debridement were included in regression analysis, which was based on a 90% development sample. The model was validated on a hold-out 10% data sample. Results: The original dataset included 26,713 VLUs, of which 11,773 ulcers were eligible for preliminary analysis and 10,942 ulcers were eligible for regression analysis. The 90% development model included 9,898 ulcers, of which 7,498 healed (75.8%). The 10% validation sample included 1,044 ulcers, of which 809 healed (77.5%). The following variables significantly predicted healing: number of concurrent wounds of any etiology, wound size, wound age (in days), evidence of bioburden/infection, being nonambulatory, and hospitalization for any reason. Innovation: The VLU Wound Healing Index (WHI) is a comprehensive, validated risk stratification model for predicting VLU healing that incorporates patient- and wound-specific variables. Conclusions: The WHI can identify which VLUs most likely require adjunctive therapies to heal, prioritize referral to venous experts, risk-stratify ulcers to create more generalizable clinical trials and understand the impact of clinical interventions. The Centers for Medicare and Medicaid Services accepts this method for reporting VLU outcome under the Quality Payment Program.
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Project description:BackgroundThe study aimed to evaluate the effects of Acacia honey (AH) on the migration, differentiation and healing properties of the cultured rabbit corneal fibroblasts.MethodsStromal derived corneal fibroblasts from New Zealand White rabbit (n = 6) were isolated and cultured until passage 1. In vitro corneal ulcer was created using a 4 mm corneal trephine onto confluent cultures and treated with basal medium (FD), medium containing serum (FDS), with and without 0.025 % AH. Wound areas were recorded at day 0, 3 and 6 post wound creation. Genes and proteins associated with wound healing and differentiation such as aldehyde dehydrogenase (ALDH), vimentin, alpha-smooth muscle actin (α-SMA), collagen type I, lumican and matrix metalloproteinase 12 (MMP12) were evaluated using qRT-PCR and immunocytochemistry respectively.ResultsCells cultured with AH-enriched FDS media achieved complete wound closure at day 6 post wound creation. The cells cultured in AH-enriched FDS media increased the expression of vimentin, collagen type I and lumican genes and decreased the ALDH, α-SMA and MMP12 gene expressions. Protein expression of ALDH, vimentin and α-SMA were in accordance with the gene expression analyses.ConclusionThese results demonstrated AH accelerate corneal fibroblasts migration and differentiation of the in vitro corneal ulcer model while increasing the genes and proteins associated with stromal wound healing.
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Project description:Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.
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Project description:BackgroundRecovery from a foot ulcer is compromised in a diabetic status, due to the impaired tissue microenvironment that consists of altered inflammation, angiogenesis and fibrosis. Phenotypic alterations in both macrophages and fibroblasts have been detected in the diabetic wound. Recently, a fibroblast subpopulation that expresses high matrix metalloproteinase 1 (MMP1), MMP3, MMP11 and Chitinase-3-Like Protein 1 (CHI3L1) was associated with a successful diabetic wound healing. However, it is not known whether these healing-associated fibroblasts are regulated by macrophages.Methods and resultsWe used bioinformatic tools to analyze selected public databases on normal and diabetic skin from patients, and identified genes significantly altered in diabetes. In a mouse model for diabetic wound healing, we detected not only a loss of the spatiotemporal changes in interleukin 1β (IL1β), IL6, IL10 and vascular endothelial growth factor A (VEGF-A) in wound macrophages, but also a compromised expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in healing-associated wound fibroblasts in a diabetic status. Co-culture with diabetic macrophages significantly reduced the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from non-diabetic wound. Co-culture with non-diabetic macrophages or diabetic macrophages supplied with IL6 significantly increased the expression of MMP1, MMP3, MMP11, CHI3L1 and VEGF-A in fibroblasts from diabetic wound. Moreover, macrophage-specific expression of IL6 significantly improved wound healing and angiogenesis in diabetic mice.ConclusionsMacrophages may induce the activation of wound-healing-associated fibroblasts, while the defective macrophages in diabetes may be corrected with IL6 treatment as a promising therapy for diabetic foot disease.
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Project description:Utilizing photothermal hydrogels as a wound dressing is a promising strategy to accelerate wound healing. Usually, a photothermal hydrogel has a strong light-absorbing capability, and hence its transparency can be largely sacrificed, which is unbeneficial for the visual monitoring of wound states. It remains challenging to balance the trade-off between the photothermal conversion and wound visualization for the photothermal hydrogel dressing. Herein, a composite photothermal hydrogel film with high transparency is presented for the visual monitor of the wound, which is constructed by incorporating CsxWO3 nanorods into the networks of polyacrylamide hydrogels. The composite photothermal hydrogel film exhibits high light absorption in the near-infrared region and high transmittance in the visible light region. Under 980 nm laser irradiation, the composite hydrogel can be heated up to 45 °C. In vivo animal experiment on mouse skin wound model shows that the composite hydrogel film can locally heat the skin wound to accelerate healing while maintaining more than 70% transparency to realize real-time observation of the wound. This study provides the first attempt to solve the problem of opacity in photothermal hydrogel dressings, promoting the possibility of its clinical applications.
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Project description:Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.
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