Publications (38) View all
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Article: Effects of angiotensin II blockade on cardiomyocyte regeneration after myocardial infarction in rats.
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ABSTRACT: INTRODUCTION: We studied the effects of angiotensin type 1 receptor blockade (ARB) on formation of new cardiomyocytes, neovascularization and ventricular remodelling after myocardial infarction (MI). METHODS: Male Wistar rats with MI or sham-operated controls were treated with either losartan or vehicle. Bromodeoxyuridine (BrdU) was given to identify newly formed cardiac cells. Immunohistochemical analysis was used to quantify proliferative and apoptotic cardiomyocytes, vascular structures and c-Kit+ stem/progenitor cells, western blotting to evaluate gene expression, and planimetry and echocardiography to assess cardiac structure and function. RESULTS: The number of BrdU+ cardiomyocytes increased similarly in the vehicle and losartan treated MI groups. The number of apoptotic or proliferating cardiomyocytes did not differ between losartan and vehicle treated rats. Losartan induced an increase in capillary and BrdU+ vascular densities in the infarct border zone. Losartan treatment completely prevented post-MI cardiac hypertrophy. In the non-infarcted myocardium the amount of all BrdU+ cells (including non-cardiomyocyte cells) was highest in the vehicle treated MI rats at week 4. CONCLUSIONS: The number of newly formed cardiomyocytes increased after MI. Angiotensin II blockade neither stimulated nor prevented cardiomyocyte regeneration. ARB treatment increased vascular densities in the infarct border zone and modulated remodelling of the non-infarcted myocardium preventing effectively post-MI cardiac hypertrophy.Journal of Renin-Angiotensin-Aldosterone System 04/2013; · 2.44 Impact Factor -
Article: Recombinant human collagen III gel for transplantation of autologous skin cells in porcine full-thickness wounds.
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ABSTRACT: Complex skin wounds, such as chronic ulcers and deep burns, require lengthy treatments and cause extensive burdens on healthcare and the economy. Use of biomaterials and cell transplantation may improve traditional treatments and promote the healing of difficult-to-treat wounds. In this study, we investigated the use of recombinant human collagen III (rhCol-III) gel as a delivery vehicle for cultured autologous skin cells (keratinocytes only or keratinocyte-fibroblast mixtures). We examined its effect on the healing of full-thickness wounds in a porcine wound-healing model. Two Landrace pigs were used for the study. Fourteen deep dermal wounds were created on the back of each pig with an 8 mm biopsy punch. Syringes containing acellular rhCol-III gel (n = 8) or rhCol-III gel with autologous keratinocytes (n = 8) or rhCol-III gel with autologous keratinocytes and fibroblasts (n = 8) were applied into wounds. Untreated wounds were used as controls for the treatment groups (n = 4). We used rhCol-III gel to manufacture a cell-delivery syringe containing autologous skin cells. In a full-thickness wound-healing model, we observed that rhCol-III gel enhances early granulation tissue formation. Interestingly, we found cell type-dependent differences in the stability of rhCol-III in vivo. Fibroblast-containing gel was effectively removed from the wound, whereas gels without cells or with keratinocytes only remained intact. Our results demonstrate that the properties of rhCol-III gel for skin cell transplantation can be significantly altered in a cell type-dependent manner. Copyright © 2013 John Wiley & Sons, Ltd.Journal of Tissue Engineering and Regenerative Medicine 01/2013; · 3.28 Impact Factor -
Article: Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
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ABSTRACT: Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing. Although NPWT has been studied as a treatment for wound closure and healing, the molecular mechanisms explaining its therapeutic effects remain unclear. To investigate the effect of NPWT on gene expression, and to discover the genes most dominantly responding to this treatment during skin wound healing, we applied negative pressure on split-thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Biopsies were collected from 4 NPWT-treated and 2 control patients. Two biopsy samples were taken from each patient: one from intact skin before graft harvesting, and one on the seventh POD from the donor site wound. Genome-wide microarrays were performed on all samples. Gene expression changes on the seventh POD were compared between NPWT and control patients, and were analyzed for statistical significance. In addition, we analyzed wound exudates for volume, and for concentrations of leukocytes, erythrocytes, and haemoglobin. NPWT induced major changes in gene expression during healing. These changes ranged from 10-fold induction to 27-fold suppression. The genes most induced were associated with cell proliferation and inflammation, and the most down-regulated genes were linked to epidermal differentiation. Our results provide the first insight into the molecular mechanisms behind NPWT, and suggest that NPWT enhances specific inflammatory gene expression at the acute phase associated with epithelial migration and wound healing. However, its continued use may inhibit epithelial differentiation.Burns: journal of the International Society for Burn Injuries 11/2012; · 1.95 Impact Factor -
Article: Human skin transcriptome during superficial cutaneous wound healing.
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ABSTRACT: Healing of the epidermis is a crucial process for maintaining the skin's defense integrity and its resistance to environmental threats. Compromised wound healing renders the individual readily vulnerable to infections and loss of body homeostasis. To clarify the human response of reepithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. In all, 25 biopsies from eight patients qualified for the study. All samples were analyzed by genome-wide microarrays. Here, we identified the genes associated with normal skin reepithelialization over time and organized them by similarities according to their induction or suppression patterns during wound healing. Our results provide the first elaborate insight into the transcriptome during normal human epidermal wound healing. The data not only reveal novel genes associated with epidermal wound healing but also provide a fundamental basis for the translational interpretation of data acquired from experimental models.Wound Repair and Regeneration 10/2012; · 2.91 Impact Factor -
Article: Improved skin wound epithelialization by topical delivery of soluble factors from fibroblast aggregates.
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ABSTRACT: Timely coverage of an excised burn wound with a split-thickness skin graft, and efficient epithelialization at the donor site wound are key components in the treatment of burn patients. Prompt healing is dependent on paracrine support from underlying dermal connective tissue fibroblasts. Using the skin graft donor site in pig as a model for epithelialization, our aim was to evaluate if dermal signals, derived from cultured dermal fibroblast aggregates (Finectra), can promote epidermal regeneration. Partial-thickness skin wounds were made with a dermatome on the backs of three domestic pigs. After randomization, topical treatment was initiated by application of Finectra (n=6) or factors from standard fibroblast monolayer cultures (n=6) trapped in a slow-clotting fibrin matrix. Saline was applied to contralateral wounds to serve as corresponding untreated controls (n=12). After 3 days, full-thickness skin samples representing the whole wound area were obtained. Histological sections of these samples were analyzed for epithelialization, cell migration from lateral wound edges and hair follicles, as well as for formation of granulation tissue. In response to topical delivery of Finectra, a significant acceleration of epithelialization (p<0.001) across the wound surface as well as from the wound edges was evident. Marked increase in thickness of granulation tissue (p<0.001) was noted in wounds treated with Finectra. Epihelialization originated from adnexal structures in which epithelial islets showed positive staining for cytokeratin-14 and PCNA. These data show that the fibroblast aggregate-derived paracrine mediators, Finectra, stimulate epidermal regeneration in vivo.Burns: journal of the International Society for Burn Injuries 11/2011; 38(4):541-50. · 1.95 Impact Factor
