Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing

AbstractStructural properties of biomaterials play critical roles in guiding cell behaviors and influence the immune response against them. We fabricated electrospun membranes with three types of surface topography (Random, Aligned, and Latticed). The aligned membranes showed immunomodulatory ability, and led to faster wound healing, reduced fibrotic response and enhanced regeneration of cutaneous appendages when used in skin wound repair. Based on that, we performed single-cell RNA sequencing analysis on cells from wounded mouse skin in the presence or absence of the Aligned scaffold. Keratinocytes, fibroblasts, and immune cells including neutrophils, monocytes, macrophages, dendritic cells, and T cells showed diverse cellular heterogeneity. More hair follicle progenitor cells, inner root sheath cells (anagen-related) and fibroblast subsets were found in the Aligned group, which corresponded to the improved regeneration of hair follicles and faster wound closure in the presence of scaffold. Immune responses towards the biomaterial differed from that of control group. In aligned samples, infiltrated macrophages and neutrophils were reduced, whereas more effector T cells were recruited. The time course of immune response was possibly advanced towards an adaptive immunity-dominant stage by the scaffold. The microenvironment around scaffold involved intricate interplay of immune cells and cutaneous cells, and wound healing was the comprehensive results of numerous influencing factors working together.

Download Full-text

Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts

International Journal of Molecular Sciences ◽

10.3390/ijms22041933 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1933

Author(s):

Paula O. Cooper ◽

MaryEllen R. Haas ◽

Satish kumar R. Noonepalle ◽

Brett A. Shook

Keyword(s):

Immune Response ◽

Wound Healing ◽

Immune Cells ◽

Inflammatory Responses ◽

Skin Wound ◽

Cellular Communication ◽

Major Contributor ◽

Inflammatory Signaling ◽

Skin Wound Healing ◽

Robust Immune Response

Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.

Download Full-text

The effect of Silver Nanoparticle Induced Diabetic on Wound Healing Full Thickness Pseudomonas aeruginosa Contaminated Mouse Skin Wound Models

International Journal of Pharmaceutical Quality Assurance ◽

10.25258/ijpqa.10.4.29 ◽

2019 ◽

Vol 10 (04) ◽

pp. 720-724

Author(s):

Thamer Mutlag Jasim ◽

Abas Adel Latif

Keyword(s):

Pseudomonas Aeruginosa ◽

Wound Healing ◽

Silver Nanoparticle ◽

Mouse Skin ◽

Treated Group ◽

Skin Wound ◽

Control Group ◽

Diabetic Wound ◽

Ag Nps ◽

Study Results

This research was considered to evaluate the antidiabetic effect of silver nanoparticle (AgNps)and following experimental diabetic. In the present study. Thirty healthy swiss mice aged between 7-8 weeks, old male mice and divided into six groups of five animals. Diabetic induced mice by using intraperitoneal (IP) injection of alloxan (180 mg lkg). Group 1 included non diabetic control, Group 2 Diabetic, Group 3 Diabetic +0.01 mg AgNps Group 4 Diabetic +0.05 AgNps, Group 5 Diabetic+ wound contaminated with Pseudomonas aeruginosa. Group 6 ( diabetic +contaminated wound + silver nanoparticle (Ag Nps). Silver nanoparticle show ample antibacterial activities. The result of the current study introduced an invivo silvernanoparticle accelerate by effects on the treatment of Pseudomonas aeruginosa infected skin wound. The present study was conducted to synthesis the AgNps biologically and evaluate its antibacterial activity against Pseudomonas aeruginosa diabetes induced by Alloxan in mice. Adminstration of silver nanoparticle resulted in significance antidiabetic effects that is is improved glucose tolerance higher source. The current study results are presented for the first time which suggest for the development of AgNps as anantdiabetic factor in future. The broad spectrum of bioactivity of AgNPs makes them promising agent not only to fight infection, but to sterile the wound and accelerate wound healing. There were significant higher wound healing scores in Nanoparticle treated group. Compared with control group. These result suggest that nanoparticle may be useful in diabetic wound healing. Treatment with asingle dose of AGNPs produced amild reduction in blood glucose and some reduction in plasma insulin at 2 h.The present results revealed the potential of the synthesized Ag-NPs as safer bactericidal agents for the treatment of diabetes induced wound contaminated with P.aeruginosa.

Download Full-text

The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke

Journal of Neuroinflammation ◽

10.1186/s12974-020-02057-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Tian-Yu Lei ◽

Ying-Ze Ye ◽

Xi-Qun Zhu ◽

Daniel Smerin ◽

Li-Juan Gu ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Immune System ◽

Immune Responses ◽

Ischaemic Stroke ◽

Immune Cells ◽

Tissue Injury ◽

Recovery Period ◽

Vital Functions ◽

Anti Inflammatory

AbstractThrough considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

Download Full-text

Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽

10.3390/cells10051004 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1004

Author(s):

Sonia Kiran ◽

Vijay Kumar ◽

Santosh Kumar ◽

Robert L Price ◽

Udai P. Singh

Keyword(s):

Insulin Resistance ◽

Immune Response ◽

T Cells ◽

Immune Cells ◽

Metabolic Diseases ◽

Liver Disorder ◽

Low Grade ◽

Peripheral Tissues ◽

Nonalcoholic Fatty Liver ◽

Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

Download Full-text

Contribution of Invariant Natural Killer T Cells to Skin Wound Healing

American Journal Of Pathology ◽

10.1016/j.ajpath.2015.08.012 ◽

2015 ◽

Vol 185 (12) ◽

pp. 3248-3257 ◽

Cited By ~ 13

Author(s):

Hiromasa Tanno ◽

Kazuyoshi Kawakami ◽

Masae Ritsu ◽

Emi Kanno ◽

Aiko Suzuki ◽

...

Keyword(s):

Wound Healing ◽

T Cells ◽

Natural Killer ◽

Natural Killer T Cells ◽

Skin Wound ◽

Skin Wound Healing ◽

Killer T Cells ◽

Invariant Natural Killer ◽

Natural Killer T

Download Full-text

IMMU-44. AN IMMUNOTHERAPEUTIC VACCINE COMPOSED OF IRRADIATED WHOLE TUMOR CELLS PULSED WITH MANNAN-BAM, TLR LIGANDS AND ANTI-CD40 ANTIBODY INDUCES POTENT IMMUNE RESPONSE IN PRECLINICAL GBM ANIMAL MODEL

Neuro-Oncology ◽

10.1093/neuonc/noab196.403 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi102-vi102

Author(s):

Herui Wang ◽

Rogelio Medina ◽

Juan Ye ◽

Pashayar Lookian ◽

Ondrej Uher ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Tumor Cells ◽

T Lymphocyte ◽

Cd8 T Cells ◽

Therapeutic Efficacy ◽

Poly I:C ◽

Control Group ◽

Complete Regression ◽

Adaptive Immune

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.

Download Full-text

EFFECTS OF PROBIOTICS SUPPLEMENTATION ON SKIN WOUND HEALING IN DIABETIC RATS

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-672020190001e1498 ◽

2020 ◽

Vol 33 (1) ◽

Author(s):

Letícia Fuganti CAMPOS ◽

Eliane TAGLIARI ◽

Thais Andrade Costa CASAGRANDE ◽

Lúcia de NORONHA ◽

Antônio Carlos L. CAMPOS ◽

...

Keyword(s):

Diabetes Mellitus ◽

Wound Healing ◽

Type I Collagen ◽

Chronic Wounds ◽

Skin Wound ◽

Diabetic Rats ◽

Control Group ◽

Type I ◽

Collagen Deposition ◽

Skin Wound Healing

ABSTRACT Background: Chronic wounds in patients with Diabetes Mellitus often become incurable due to prolonged and excessive production of inflammatory cytokines. The use of probiotics modifies the intestinal microbiota and modulates inflammatory reactions. Aim: To evaluate the influence of perioperative supplementation with probiotics in the cutaneous healing process in diabetic rats. Methods: Forty-six rats were divided into four groups (C3, P3, C10, P10) according to the treatment (P=probiotic or C=control, both orally administered) and day of euthanasia, 3rd or 10th postoperative days. All rats were induced to Diabetes Mellitus 72 h before starting the experiment with alloxan. Supplementation was initiated five days before the incision and maintained until euthanasia. Scalpel incision was guided by a 2x2 cm mold and the wounds were left to heal per second-intention. The wounds were digitally measured. Collagen densitometry was done with Picrosirius Red staining. Histological parameters were analyzed by staining by H&E. Results: The contraction of the wound was faster in the P10 group which resulted in a smaller scar area (p=0.011). There was an increase in type I collagen deposition from the 3rd to the 10th postoperative day in the probiotic groups (p=0.016), which did not occur in the control group (p=0.487). The histological analysis showed a better degree of healing in the P10 group (p=0.005), with fewer polymorphonuclear (p<0.001) and more neovessels (p=0.001). Conclusions: Perioperative supplementation of probiotics stimulates skin wound healing in diabetic rats, possibly due to attenuation of the inflammatory response and increased neovascularization and type I collagen deposition.

Download Full-text

Whole Blood Transcriptome Analysis Reveals Positive Effects of Dried Olive Pomace-Supplemented Diet on Inflammation and Cholesterol in Laying Hens

Animals ◽

10.3390/ani9070427 ◽

2019 ◽

Vol 9 (7) ◽

pp. 427 ◽

Cited By ~ 7

Author(s):

Marco Iannaccone ◽

Andrea Ianni ◽

Solange Ramazzotti ◽

Lisa Grotta ◽

Elettra Marone ◽

...

Keyword(s):

Immune Response ◽

Laying Hens ◽

Cholesterol Biosynthesis ◽

Control Group ◽

Sequencing Analysis ◽

Olive Pomace ◽

Positive Effects ◽

Diet Control ◽

Productive Traits ◽

Olive Industry

Olive pomace (OP) represents one of the by-products of the olive industry and represents an important source of bioactive compounds. This characteristic makes OP a potential feed supplement in livestock nutrition. Thus, in the last years, several studies have been published to evaluate the productive traits following OP supplementation in animal diets; however, relatively little is known from a molecular biology standpoint. Therefore, in this study, we report the RNA-sequencing analysis of laying hens fed with a 10% dried OP (DOP) supplementation. Applying a false discovery rate (FDR) <0.05 and a Log2Fc either less than −1.5 or higher than +1.5, we identified 264 differentially regulated genes (DEGs) between the non-supplemented diet control group (CTR) and the DOP group. Using the 264 DEGs to identify enriched biological pathways, we noted that cholesterol biosynthesis showed the highest enrichment followed by several pathways related to immune response and inflammation. As a consequence, when we quantified the cholesterol amount in yolk egg, we found a significant reduction in the DOP vs. the CTR group (p < 0.05). In conclusion, this study shows that DPO affects gene expression in laying hens, which is directly correlated with cholesterol decrease and can potentially ameliorate health status influencing immune response and inflammation.

Download Full-text

Topical hydrogel containing Fumaria vaillantii Loisel. extract enhances wound healing in rats

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2645-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Fatemeh Davoodi-Roodbordeii ◽

Minoo Afshar ◽

Fatemeh Haji Abas Tabrizi ◽

Samira Choopani ◽

Giti Torkaman ◽

...

Keyword(s):

Wound Healing ◽

Breaking Strength ◽

Negative Control ◽

Skin Wound ◽

Hair Follicles ◽

Uniaxial Tensile ◽

Total Extract ◽

Collagen Formation ◽

Significant Difference ◽

Incision Wound

Abstract Background Fumaria species (Fumariacea) has traditionally been used in wound healing in Iranian folk medicine. However, with the discovery of newer agents, its use has faded off into total obscurity. This study explored the wound healing potential of a gel containing 10% Fumaria vaillantii Loisel through topical application of total extract in a model of excisional as well as incisional wound healing in albino Wistar rats. Methods Rats were anesthetized, and excisional skin wound was established using a sterilized surgical scissors. The animals were then treated with 10% F.vaillantii topical gel formulation along with the gel base. The treatments were administered once a day after the injury for 21 days. For topical treatment, the hydrogel was formulated and evaluated for chemical and physical characteristics. Histopathological analysis with hematoxylin and eosin (H&E) was used for microscopic examination of the skin tissues on 21-day-old sections of excision wound. To verify collagen formation, hydroxyproline determination was performed 21 days post wound healing. Breaking strength was determined in a 10-day-old incision wound by the uniaxial tensile test. Results Topical administration of F.vaillantii gel formulation significantly enhanced skin wound closure on the 6th post-wounding day compared to both gel base and the negative control, indicating an accelerated wound healing process, while a significant difference was observed on 10th and 14th post –wound days in F.vaillantii treatment compared to the negative control groups. Gel formulation prepared with a 10% F. vaillantii extract exhibited a response in terms of wound epithelialization, angiogenesis and number of hair follicles at wound area better than the gel base on the 21st post-wound day. Application of gel base produced further advantages by increasing hydroxyproline content and collagen fiber thickness. Our results on incision wound model were supported by histopathological data indicating the role of gel base in the enhancement of breaking strength. Conclusion Traditional use of Fumaria species in the skin diseases was justified in this study by revealing the increase in wound healing activity after hydrogel containing F. vaillantii total extract administration. Graphical abstract

Download Full-text