Sepsis, a dysregulated response to infection, is a leading cause of death after burn injury. Changes in the immune response as well as the loss of the skin, the primary barrier to infection, contribute to the increased risk for infection and sepsis in burn patients. This higher risk is further compounded by the development of the systemic inflammatory response and hypermetabolic state, which limit the utility of commonly used infection markers. As such, the development of sepsis biomarkers after burn injury is an imperative. A sepsis biomarker would facilitate earlier diagnosis and treatment of sepsis, thus decreasing length of stay, morbidity, and mortality after burn injury. Numerous different biomarkers, ranging from acute phase reactants, cytokines, and inflammatory markers to omics analyses and extracellular vesicles have been assessed as potential biomarkers in burn sepsis. To date no single biomarker has proven useful as the sole indicator for sepsis. The future of burn sepsis biomarkers will likely require a panel of biomarkers from all categories. The purpose of this review article is to list the various biomarkers that have been studied in burn sepsis and describe their clinical utility and future use in patients with burn injury.
{"title":"Biomarkers of sepsis in burn injury: an update","authors":"Tina L Palmieri, Jason Heard","doi":"10.1093/burnst/tkae080","DOIUrl":"https://doi.org/10.1093/burnst/tkae080","url":null,"abstract":"Sepsis, a dysregulated response to infection, is a leading cause of death after burn injury. Changes in the immune response as well as the loss of the skin, the primary barrier to infection, contribute to the increased risk for infection and sepsis in burn patients. This higher risk is further compounded by the development of the systemic inflammatory response and hypermetabolic state, which limit the utility of commonly used infection markers. As such, the development of sepsis biomarkers after burn injury is an imperative. A sepsis biomarker would facilitate earlier diagnosis and treatment of sepsis, thus decreasing length of stay, morbidity, and mortality after burn injury. Numerous different biomarkers, ranging from acute phase reactants, cytokines, and inflammatory markers to omics analyses and extracellular vesicles have been assessed as potential biomarkers in burn sepsis. To date no single biomarker has proven useful as the sole indicator for sepsis. The future of burn sepsis biomarkers will likely require a panel of biomarkers from all categories. The purpose of this review article is to list the various biomarkers that have been studied in burn sepsis and describe their clinical utility and future use in patients with burn injury.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"10 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jane Sun, Imaan Ahmed, Jason Brown, Kiarash Khosrotehrani, Abbas Shafiee
Background Rodent models have been widely used to investigate skin development, but do not account for significant differences in composition compared to human skin. On the other hand, two-dimensional and three-dimensional engineered skin models still lack the complex features of human skin such as appendages and pigmentation. Recently, hair follicle containing skin organoids (SKOs) with a stratified epidermis, and dermis layer have been generated as floating spheres from human-induced pluripotent stem cells (hiPSCs). Methods The current study aims to investigate the generation of hiPSCs-derived SKOs using an air-liquid interface (ALI) model on transwell membranes (T-SKOs) and compares their development with conventional floating culture in low-attachment plates (F-SKOs). Results Mature SKOs containing an epidermis, dermis, and appendages are created in both T-SKO and F-SKO conditions. It was found that the hair follicles are smaller and shorter in the F-SKO compared with T-SKOs. Additionally, the ALI conditions contribute to enhanced hair follicle numbers than conventional floating culture. Conclusions Together, this study demonstrates the significant influence of transwell culture on the morphogenesis of hair follicles within SKOs and highlights the potential for refinement of skin model engineering for advancing dermatology and skin research.
{"title":"The empowering influence of air-liquid interface culture on skin organoid hair follicle development","authors":"Jane Sun, Imaan Ahmed, Jason Brown, Kiarash Khosrotehrani, Abbas Shafiee","doi":"10.1093/burnst/tkae070","DOIUrl":"https://doi.org/10.1093/burnst/tkae070","url":null,"abstract":"Background Rodent models have been widely used to investigate skin development, but do not account for significant differences in composition compared to human skin. On the other hand, two-dimensional and three-dimensional engineered skin models still lack the complex features of human skin such as appendages and pigmentation. Recently, hair follicle containing skin organoids (SKOs) with a stratified epidermis, and dermis layer have been generated as floating spheres from human-induced pluripotent stem cells (hiPSCs). Methods The current study aims to investigate the generation of hiPSCs-derived SKOs using an air-liquid interface (ALI) model on transwell membranes (T-SKOs) and compares their development with conventional floating culture in low-attachment plates (F-SKOs). Results Mature SKOs containing an epidermis, dermis, and appendages are created in both T-SKO and F-SKO conditions. It was found that the hair follicles are smaller and shorter in the F-SKO compared with T-SKOs. Additionally, the ALI conditions contribute to enhanced hair follicle numbers than conventional floating culture. Conclusions Together, this study demonstrates the significant influence of transwell culture on the morphogenesis of hair follicles within SKOs and highlights the potential for refinement of skin model engineering for advancing dermatology and skin research.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqin Huang, Haoran Zhang, Yuhong Luo, Xin Yi, Zengding Zhou, Feng Guo, Lei Yi
Background Lipopolysaccharide (LPS)-induced apoptosis of lung microvascular endothelial cells (ECs) is the main reason of lung edema and acute lung injury (ALI) in septic conditions. Telocytes (TCs) are a distinct type of interstitial cells found around the lung microvasculature, which may protect ECs through the release of shed vesicles. However, whether TCs protect against LPS-induced EC apoptosis and ALI has not been determined. Methods The protective effects of TCs on ECs were assessed in vitro using transwell assays and flow cytometry, and in vivo using an LPS-induced mouse ALI model. RNA sequencing was used to identify miRNA-146a-5p as a key component of TC-derived exosomes. The functions of miRNA-146a-5p were further evaluated by western blotting, flow cytometry, and transendothelial electrical resistance measurements. Results We demonstrated that LPS stimulation induced the secretion of active exosomes from TCs, which inhibited LPS-mediated apoptosis of ECs and reduced ALI in mice. Moreover, miRNA-146a-5p was identified as the main bioactive molecule in TC-derived exosomes, capable of inhibiting LPS-induced caspase-3 activation and apoptosis in ECs. Conclusions Our results indicate that TCs effectively prevent LPS-induced EC apoptosis and ALI through the release of exosomes, with subsequent activation of the miRNA-146a-5p/caspase-3 signaling pathway in ECs.
{"title":"Lipopolysaccharide-induced active telocyte exosomes alleviate lipopolysaccharide-induced vascular barrier disruption and acute lung injury via the activation of the miRNA-146a-5p/caspase-3 signaling pathway in endothelial cells","authors":"Xiaoqin Huang, Haoran Zhang, Yuhong Luo, Xin Yi, Zengding Zhou, Feng Guo, Lei Yi","doi":"10.1093/burnst/tkae074","DOIUrl":"https://doi.org/10.1093/burnst/tkae074","url":null,"abstract":"Background Lipopolysaccharide (LPS)-induced apoptosis of lung microvascular endothelial cells (ECs) is the main reason of lung edema and acute lung injury (ALI) in septic conditions. Telocytes (TCs) are a distinct type of interstitial cells found around the lung microvasculature, which may protect ECs through the release of shed vesicles. However, whether TCs protect against LPS-induced EC apoptosis and ALI has not been determined. Methods The protective effects of TCs on ECs were assessed in vitro using transwell assays and flow cytometry, and in vivo using an LPS-induced mouse ALI model. RNA sequencing was used to identify miRNA-146a-5p as a key component of TC-derived exosomes. The functions of miRNA-146a-5p were further evaluated by western blotting, flow cytometry, and transendothelial electrical resistance measurements. Results We demonstrated that LPS stimulation induced the secretion of active exosomes from TCs, which inhibited LPS-mediated apoptosis of ECs and reduced ALI in mice. Moreover, miRNA-146a-5p was identified as the main bioactive molecule in TC-derived exosomes, capable of inhibiting LPS-induced caspase-3 activation and apoptosis in ECs. Conclusions Our results indicate that TCs effectively prevent LPS-induced EC apoptosis and ALI through the release of exosomes, with subsequent activation of the miRNA-146a-5p/caspase-3 signaling pathway in ECs.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the past two decades, record-breaking heat waves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a life-threatening systemic condition characterized by a core body temperature >40°C and the subsequent development of multiple organ dysfunction syndrome. Lung injury is a well-documented complication of heatstroke and is usually the secondary cause of patient death. In recent years, extensive research has been conducted to investigate the underlying causes of heatstroke and heatstroke-induced lung injury. This review aims to consolidate and present the current understanding of the key pathogenic mechanisms involved in heatstroke and heatstroke-induced lung injury. In addition, systemic factors such as heat cytotoxicity, systemic inflammation, oxidative stress, endothelial cell dysfunction, and other factors are involved in the pathogenesis of lung injury in heatstroke. Furthermore, we also established current management strategies for heatstroke and heatstroke-induced lung injury. However, further investigation is required to fully understand the detailed pathogenesis of heatstroke so that potentially effective means of treating and preventing heatstroke and heatstroke-induced lung injury can be developed and studied.
{"title":"The pathogenesis and management of heatstroke and heatstroke-induced lung injury","authors":"Jian Liu, Qin Li, Zhimin Zou, Li Li, Zhengtao Gu","doi":"10.1093/burnst/tkae048","DOIUrl":"https://doi.org/10.1093/burnst/tkae048","url":null,"abstract":"In the past two decades, record-breaking heat waves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a life-threatening systemic condition characterized by a core body temperature >40°C and the subsequent development of multiple organ dysfunction syndrome. Lung injury is a well-documented complication of heatstroke and is usually the secondary cause of patient death. In recent years, extensive research has been conducted to investigate the underlying causes of heatstroke and heatstroke-induced lung injury. This review aims to consolidate and present the current understanding of the key pathogenic mechanisms involved in heatstroke and heatstroke-induced lung injury. In addition, systemic factors such as heat cytotoxicity, systemic inflammation, oxidative stress, endothelial cell dysfunction, and other factors are involved in the pathogenesis of lung injury in heatstroke. Furthermore, we also established current management strategies for heatstroke and heatstroke-induced lung injury. However, further investigation is required to fully understand the detailed pathogenesis of heatstroke so that potentially effective means of treating and preventing heatstroke and heatstroke-induced lung injury can be developed and studied.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Precision immunotherapy signifies the administration of the required type of immune intervention tailored to the state of immune activation at the appropriate time window. The classification of patients into the different states of immune activation is usually done by either a protein blood biomarker or a molecular blood endotype that is diagnostic of the precise immune state. Evidence coming from trials of the last decade suggests that immune interventions should be split into strategies aiming to attenuate the exaggerated immune responses, restore sepsis-induced immunoparalysis (SII) and restore the vascular tone. Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab. Biomarkers that guide their use are ferritin, soluble triggering receptor expressed on myeloid cells-1 and C-reactive protein. Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials.
{"title":"Recent advances of precision immunotherapy in sepsis.","authors":"Antonios Arapis, Dimitrios Panagiotopoulos, Evangelos J Giamarellos-Bourboulis","doi":"10.1093/burnst/tkaf001","DOIUrl":"10.1093/burnst/tkaf001","url":null,"abstract":"<p><p>Precision immunotherapy signifies the administration of the required type of immune intervention tailored to the state of immune activation at the appropriate time window. The classification of patients into the different states of immune activation is usually done by either a protein blood biomarker or a molecular blood endotype that is diagnostic of the precise immune state. Evidence coming from trials of the last decade suggests that immune interventions should be split into strategies aiming to attenuate the exaggerated immune responses, restore sepsis-induced immunoparalysis (SII) and restore the vascular tone. Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab. Biomarkers that guide their use are ferritin, soluble triggering receptor expressed on myeloid cells-1 and C-reactive protein. Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials.</p>","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"13 ","pages":"tkaf001"},"PeriodicalIF":6.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aryna Kolodyazhna, W Joost Wiersinga, Tom van der Poll
According to the latest definition, sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to an infection. However, this definition fails to grasp the heterogeneous nature and the underlying dynamic pathophysiology of the syndrome. In response to this heterogeneity, efforts have been made to stratify sepsis patients into subtypes, either based on their clinical presentation or pathophysiological characteristics. Subtyping introduces the possibility of the implementation of personalized medicine, whereby each patient receives treatment tailored to their individual disease manifestation. This review explores the currently known subtypes, categorized by subphenotypes and endotypes, as well as the treatments that have been researched thus far in the context of sepsis subtypes and personalized medicine.
{"title":"Aiming for precision: personalized medicine through sepsis subtyping","authors":"Aryna Kolodyazhna, W Joost Wiersinga, Tom van der Poll","doi":"10.1093/burnst/tkae073","DOIUrl":"https://doi.org/10.1093/burnst/tkae073","url":null,"abstract":"According to the latest definition, sepsis is characterized by life-threatening organ dysfunction caused by a dysregulated host response to an infection. However, this definition fails to grasp the heterogeneous nature and the underlying dynamic pathophysiology of the syndrome. In response to this heterogeneity, efforts have been made to stratify sepsis patients into subtypes, either based on their clinical presentation or pathophysiological characteristics. Subtyping introduces the possibility of the implementation of personalized medicine, whereby each patient receives treatment tailored to their individual disease manifestation. This review explores the currently known subtypes, categorized by subphenotypes and endotypes, as well as the treatments that have been researched thus far in the context of sepsis subtypes and personalized medicine.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"36 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Effective wound management and treatment are crucial in clinical practice, yet existing strategies often fall short in fully addressing the complexities of skin wound healing. Recent advancements in tissue engineering have introduced innovative approaches, particularly through the use of nanobiomaterials, to enhance the healing process. In this context, titanium dioxide nanoparticles (TiO2 NPs) have garnered attention due to their excellent biological properties, including antioxidant, anti-inflammatory, and antimicrobial properties. Furthermore, these nanoparticles can be modified to enhance their therapeutic benefits. Scaffolds and dressings containing TiO2 NPs have demonstrated promising outcomes in accelerating wound healing and enhancing tissue regeneration. This review paper covers the wound healing process, the biological properties of TiO2 NPs that make them suitable for promoting wound healing, methods for synthesizing TiO2 NPs, the use of scaffolds and dressings containing TiO2 NPs in wound healing, the application of modified TiO2 NPs in wound healing, and the potential toxicity of TiO2 NPs.
{"title":"Titanium dioxide nanoparticles: a promising candidate for wound healing applications","authors":"Hamed Nosrati, Morteza Heydari","doi":"10.1093/burnst/tkae069","DOIUrl":"https://doi.org/10.1093/burnst/tkae069","url":null,"abstract":"Effective wound management and treatment are crucial in clinical practice, yet existing strategies often fall short in fully addressing the complexities of skin wound healing. Recent advancements in tissue engineering have introduced innovative approaches, particularly through the use of nanobiomaterials, to enhance the healing process. In this context, titanium dioxide nanoparticles (TiO2 NPs) have garnered attention due to their excellent biological properties, including antioxidant, anti-inflammatory, and antimicrobial properties. Furthermore, these nanoparticles can be modified to enhance their therapeutic benefits. Scaffolds and dressings containing TiO2 NPs have demonstrated promising outcomes in accelerating wound healing and enhancing tissue regeneration. This review paper covers the wound healing process, the biological properties of TiO2 NPs that make them suitable for promoting wound healing, methods for synthesizing TiO2 NPs, the use of scaffolds and dressings containing TiO2 NPs in wound healing, the application of modified TiO2 NPs in wound healing, and the potential toxicity of TiO2 NPs.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"21 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zitong Wang, Feng Zhao, Hongxin Lang, Haiyue Ren, Qiqi Zhang, Xing Huang, Cai He, Chengcheng Xu, Chiyu Tan, Jiajie Ma, Shu Duan, Zhe Wang
Stem cells (SCs) can self-replicate and differentiate into multiple lineages. Organoids, 3D cultures derived from SCs, can replicate the spatial structure and physiological characteristics of organs in vitro. Skin organoids can effectively simulate the physiological structure and function of skin tissue, reliably restoring the natural skin ecology in various in vitro environments. Skin organoids have been employed extensively in skin development and pathology research, offering valuable insights for drug screening. Moreover, they play crucial roles in skin regeneration and tissue repair. This in-depth review explores the construction and applications of skin organoids in wound healing, with a focus on their construction process, including skin appendage integration, and significant advancements in wound-healing research.
{"title":"Organoids in skin wound healing","authors":"Zitong Wang, Feng Zhao, Hongxin Lang, Haiyue Ren, Qiqi Zhang, Xing Huang, Cai He, Chengcheng Xu, Chiyu Tan, Jiajie Ma, Shu Duan, Zhe Wang","doi":"10.1093/burnst/tkae077","DOIUrl":"https://doi.org/10.1093/burnst/tkae077","url":null,"abstract":"Stem cells (SCs) can self-replicate and differentiate into multiple lineages. Organoids, 3D cultures derived from SCs, can replicate the spatial structure and physiological characteristics of organs in vitro. Skin organoids can effectively simulate the physiological structure and function of skin tissue, reliably restoring the natural skin ecology in various in vitro environments. Skin organoids have been employed extensively in skin development and pathology research, offering valuable insights for drug screening. Moreover, they play crucial roles in skin regeneration and tissue repair. This in-depth review explores the construction and applications of skin organoids in wound healing, with a focus on their construction process, including skin appendage integration, and significant advancements in wound-healing research.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"66 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deni Kang, Xiaoxiang Wang, Wentao Chen, Lujia Mao, Weiqiang Zhang, Yan Shi, Julin Xie, Ronghua Yang
Background Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs). Methods This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis. Results Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing. Conclusions In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.
{"title":"Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts","authors":"Deni Kang, Xiaoxiang Wang, Wentao Chen, Lujia Mao, Weiqiang Zhang, Yan Shi, Julin Xie, Ronghua Yang","doi":"10.1093/burnst/tkae047","DOIUrl":"https://doi.org/10.1093/burnst/tkae047","url":null,"abstract":"Background Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs). Methods This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis. Results Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing. Conclusions In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"43 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background The extracellular matrix (ECM) provides essential physical support and biochemical cues for diverse biological activities, including tissue remodelling and regeneration, and thus is commonly applied in the construction of artificial peripheral nerve grafts. Nevertheless, the specific functions of essential peripheral nerve ECM components have not been fully determined. Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration. Methods Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro. The cells were seeded onto noncoated dishes, Matrigel-coated dishes, and dishes coated with the four major ECM components fibronectin, laminin, collagen I, and collagen IV. The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide (MTT), Cell Counting Kit-8, and 5-ethynyl-2'-deoxyuridine (EdU) assays, whereas their effects on cell migration were determined via wound healing and live-cell imaging. Neurite growth in neurons cultured on different ECM components was observed. Furthermore, the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats. Immunofluorescence analysis and a behavioural assessment, including gait, electrophysiology, and target muscle analysis, were conducted. Results ECM components, especially collagen I, stimulated the DNA synthesis and movement of Schwann cells. Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth. Injection of collagen I into chitosan and poly(lactic-co-glycolic acid) artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels. In contrast, collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration. Conclusions These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves, reveal the contributing roles of collagen I in microenvironment construction and axon regeneration, and highlight the use of collagen I for the healing of injured peripheral nerves.
{"title":"Type I collagen extracellular matrix facilitates nerve regeneration via the construction of a favourable microenvironment","authors":"Panjian Lu, Zhiying Chen, Mingjun Wu, Shuyue Feng, Sailing Chen, Xiyang Cheng, Yahong Zhao, Xingyu Liu, Leilei Gong, Lijing Bian, Sheng Yi, Hongkui Wang","doi":"10.1093/burnst/tkae049","DOIUrl":"https://doi.org/10.1093/burnst/tkae049","url":null,"abstract":"Background The extracellular matrix (ECM) provides essential physical support and biochemical cues for diverse biological activities, including tissue remodelling and regeneration, and thus is commonly applied in the construction of artificial peripheral nerve grafts. Nevertheless, the specific functions of essential peripheral nerve ECM components have not been fully determined. Our research aimed to differentially represent the neural activities of main components of ECM on peripheral nerve regeneration. Methods Schwann cells from sciatic nerves and neurons from dorsal root ganglia were isolated and cultured in vitro. The cells were seeded onto noncoated dishes, Matrigel-coated dishes, and dishes coated with the four major ECM components fibronectin, laminin, collagen I, and collagen IV. The effects of these ECM components on Schwann cell proliferation were determined via methylthiazolyldiphenyl-tetrazolium bromide (MTT), Cell Counting Kit-8, and 5-ethynyl-2'-deoxyuridine (EdU) assays, whereas their effects on cell migration were determined via wound healing and live-cell imaging. Neurite growth in neurons cultured on different ECM components was observed. Furthermore, the two types of collagen were incorporated into chitosan artificial nerves and used to repair sciatic nerve defects in rats. Immunofluorescence analysis and a behavioural assessment, including gait, electrophysiology, and target muscle analysis, were conducted. Results ECM components, especially collagen I, stimulated the DNA synthesis and movement of Schwann cells. Direct measurement of the neurite lengths of neurons cultured on ECM components further revealed the beneficial effects of ECM components on neurite outgrowth. Injection of collagen I into chitosan and poly(lactic-co-glycolic acid) artificial nerves demonstrated that collagen I facilitated axon regeneration and functional recovery after nerve defect repair by stimulating the migration of Schwann cells and the formation of new blood vessels. In contrast, collagen IV recruited excess fibroblasts and inflammatory macrophages and thus had disadvantageous effects on nerve regeneration. Conclusions These findings reveal the modulatory effects of specific ECM components on cell populations of peripheral nerves, reveal the contributing roles of collagen I in microenvironment construction and axon regeneration, and highlight the use of collagen I for the healing of injured peripheral nerves.","PeriodicalId":9553,"journal":{"name":"Burns & Trauma","volume":"9 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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