SciCombinator

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Concept: Wound healing

223

Every element or cell in the human body produces substances that communicate and respond in an autocrine or paracrine mode, consequently affecting organs and structures that are seemingly far from each other. The same also applies to the skin. In fact, when the integrity of the skin has been altered, or when its healing process is disturbed, it becomes a source of symptoms that are not merely cutaneous. The skin is an organ, and similar to any other structure, it has different functions in addition to connections with the central and peripheral nervous system. This article examines pathological responses produced by scars, analyzing definitions and differences. At the same time, it considers the subcutaneous fascias, as this connective structure is altered when there is a discontinuous cutaneous surface. The consequence is an ample symptomatology, which is not limited to the body area where the scar is located, such as a postural or trigeminal disorder.

Concepts: Nervous system, Scar, Wound healing, Collagen, Healing, Organ, Skin, Human anatomy

173

Multipotent mesenchymal stem cells (MSCs) are found in various tissues and can proliferate extensively in vitro. MSCs have been used in preclinical animal studies and clinical trials in many fields. Adipose derived stem cells (ASCs) have several advantages compared to other MSCs for use in cell-based treatments because they are easy to isolate with relative abundance. However, quantitative approaches for wound repair using ASCs have been limited because of lack of animal models which allow for quantification. Here, we addressed the effect of topically delivered ASCs in wound repair by quantitative analysis using the rabbit ear model. We characterized rabbit ASCs, and analyzed their multipotency in comparison to bone marrow derived-MSCs (BM-MSCs) and dermal fibroblasts (DFs) in vitro. Topically delivered ASCs increased granulation tissue formation in wounds when compared to saline controls, whereas BM-MSCs or DFs did not. These studies suggest that ASCs and BM-MSCs are not identical, though they have similar surface markers. We found that topically delivered ASCs are engrafted and proliferate in the wounds. We showed that transplanted ASCs exhibited activated fibroblast phenotype, increased endothelial cell recruitment, and enhanced macrophage recruitment in vivo.

Concepts: Wound healing, Collagen, Extracellular matrix, Fibroblast, Stem cell, Mesenchymal stem cell, Bone marrow, Wound

173

BACKGROUND: Over the past decade, there has been growing interest within ethnobiology in the knowledge and practices of migrating people. Within this, scholars have given relatively less attention to displaced people and refugees: to the loss, maintenance, and adaptation of refugees' ethnobiological knowledge, and to its significance for refugees' wellbeing. This study focuses on cosmetics and remedies used to heal skin afflictions that are traditionally used by Sahrawi refugees displaced in South Western Algerian refugee camps. METHODS: The research methods included a structured survey carried out with 37 refugee households, semi-structured interviews with 77 refugees, 24 retrospective interviews with refugees and other knowledgeable informants, and a voucher specimen collection of the plants and products cited. RESULTS: We recorded the use of 55 plant species, nine animal species, and six mineral products used within the three main use categories discussed in this paper: 1) Remedies for health issues that are typical of the desert environment where the Sahrawi once lived as nomads and now live as refugees (e.g. eye afflictions); 2) Remedies for wounds that are influenced by the Sahrawi’s recent history of guerrilla warfare; and 3) Cosmetics and products used for body care, decoration and perfuming (e.g. hair care, teeth cleansing, henna use) and for aromatizing the air inside of tents and which are widely used in everyday life and social practices. CONCLUSIONS: We discuss the changes that have occurred in the patterns of use and procurement of these products with exile and sedentarization in refugee camps, and conclude that refugees are not simply passive recipients of national and international aid, but rather struggle to maintain and recover their traditional ethnobiological practices in exile. Finally, we suggest further research into the ethnobiological practices and knowledge of displaced populations.

Concepts: Wound healing, Internally displaced person, Refugee, Vietnam War, Algeria, Western Sahara, Displaced person, Polisario Front

172

Fibroblasts residing in connective tissues throughout the body are responsible for extracellular matrix (ECM) homeostasis and repair. In response to tissue damage, they activate to become myofibroblasts, which have organized contractile cytoskeletons and produce a myriad of proteins for ECM remodeling. However, persistence of myofibroblasts can lead to fibrosis with excessive collagen deposition and tissue stiffening. Thus, understanding which signals regulate de-activation of myofibroblasts during normal tissue repair is critical. Substrate modulus has recently been shown to regulate fibrogenic properties, proliferation and apoptosis of fibroblasts isolated from different organs. However, few studies track the cellular responses of fibroblasts to dynamic changes in the microenvironmental modulus. Here, we utilized a light-responsive hydrogel system to probe the fate of valvular myofibroblasts when the Young’s modulus of the substrate was reduced from ~32 kPa, mimicking pre-calcified diseased tissue, to ~7 kPa, mimicking healthy cardiac valve fibrosa. After softening the substrata, valvular myofibroblasts de-activated with decreases in α-smooth muscle actin (α-SMA) stress fibers and proliferation, indicating a dormant fibroblast state. Gene signatures of myofibroblasts (including α-SMA and connective tissue growth factor (CTGF)) were significantly down-regulated to fibroblast levels within 6 hours of in situ substrate elasticity reduction while a general fibroblast gene vimentin was not changed. Additionally, the de-activated fibroblasts were in a reversible state and could be re-activated to enter cell cycle by growth stimulation and to express fibrogenic genes, such as CTGF, collagen 1A1 and fibronectin 1, in response to TGF-β1. Our data suggest that lowering substrate modulus can serve as a cue to down-regulate the valvular myofibroblast phenotype resulting in a predominantly quiescent fibroblast population. These results provide insight in designing hydrogel substrates with physiologically relevant stiffness to dynamically redirect cell fate in vitro.

Concepts: Bone, Wound healing, Collagen, Extracellular matrix, Muscle, Tissues, Connective tissue, Young's modulus

171

Silver nanoparticles supported on nanoscale silicate platelets (AgNP/NSP) possess interesting properties, including a large surface area and high biocide effectiveness. The nanohybrid of AgNP/NSP at a weight ratio 7/93 contains 5-nm Ag particles supported on the surface of platelets with dimensions of approximately 80×80×1 nm(3). The nanohybrid expresses a trend of lower cytotoxicity at the concentration of 8.75 ppm Ag and low genotoxicity. Compared with conventional silver ions and the organically dispersed AgNPs, the nanohybrid promotes wound healing. We investigated overall wound healing by using acute burn and excision wound healing models. Tests on both infected wound models of mice were compared among the AgNP/NSP, polymer-dispersed AgNPs, the commercially available Aquacel, and silver sulfadiazine. The AgNP/NSP nanohybrid was superior for wound appearance, but had similar wound healing rates, vascular endothelial growth factor (VEGF)-A levels and transforming growth factor (TGF)-β1 expressions to Aquacel and silver sulfadiazine.

Concepts: Wound healing, Angiogenesis, Coagulation, Platelet, Nanotechnology, Silver, Surface area

169

After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues.

Concepts: Gene expression, Wound healing, Innate immune system, Skin, Serine protease, Injury, Wound, Chronic wound

169

BACKGROUND: Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. METHODS: Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-alpha an ER-beta) antibodies. RESULTS: Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-alpha an ER-beta in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-alpha and ER-beta were the highest in the ovx+YCJ group, as compared to the ovx+EB group. CONCLUSIONS: This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

Concepts: Wound healing, Healing, Estradiol, Skin, Dermis, Epidermis, Sebaceous gland, Coconut water

169

Lipomas are common benign tumours of fat cells. In most cases, surgical excision is curative and simple to perform; however, such a procedure requires general anaesthesia and may be associated with delayed wound healing, seroma formation and nerve injury in deep and intramuscular tumours. The objective of this study was to evaluate treatment of subcutaneous, subfascial or intermuscular lipomas using intralesional steroid injections in dogs. Fifteen dogs presenting with lipomas were selected for treatment with ultrasound-guided intralesional injection of triamcinolone acetonide at a dose of 40 mg/mL. Nine subcutaneous and subfascial tumours showed a complete regression. The other lipomas decreased in diameter, achieving, in some cases, remission of discomfort and regression of lameness. Steroid injection was a relatively safe and effective treatment for lipomas in dogs; only six dogs experienced polyuria/polydipsia for about 2 weeks post-treatment.

Concepts: Wound healing, Surgery, Benign tumor, Anesthesia, Injury, Al-Andalus, Excision, Triamcinolone acetonide

167

St. John’s wort (Hypericum perforatum) has been intensively investigated for its antidepressive activity, but dermatological applications also have a long tradition. Topical St. John’s wort preparations such as oils or tinctures are used for the treatment of minor wounds and burns, sunburns, abrasions, bruises, contusions, ulcers, myalgia, and many others. Pharmacological research supports the use in these fields. Of the constituents, naphthodianthrones (e.g., hypericin) and phloroglucinols (e.g., hyperforin) have interesting pharmacological profiles, including antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. In addition, hyperforin stimulates growth and differentiation of keratinocytes, and hypericin is a photosensitizer which can be used for selective treatment of nonmelanoma skin cancer. However, clinical research in this field is still scarce. Recently, sporadic trials have been conducted in wound healing, atopic dermatitis, psoriasis, and herpes simplex infections, partly with purified single constituents and modern dermatological formulations. St. John’s wort also has a potential for use in medical skin care. Composition and stability of pharmaceutical formulations vary greatly depending on origin of the plant material, production method, lipophilicity of solvents, and storage conditions, and this must be regarded with respect to practical as well as scientific purposes.

Concepts: Pharmacology, Medicine, Wound healing, Herpes simplex, Wound, St John's wort, Hypericum, Hyperforin

167

BACKGROUND: Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. HYPOTHESIS: Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. ANIMALS: Adult healthy beagle dogs (n = 10; 3-6 years old; 7.2-13.1 kg) were studied. METHODS: Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and α-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-γ, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. RESULTS: Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-γ) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). CONCLUSION AND CLINICAL IMPORTANCE: Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing.

Concepts: Wound healing, Collagen, Stem cell, Mesenchymal stem cell, Bone marrow, Stem cells, Cellular differentiation, Fibroblast growth factor