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Notizen: It has been evidenced that the fat may have a potential to secret some growth factors or be a source of stem cells. So, we explore the effects of fat on healing of porcine skin wounds so as to provide a new method for clinical skin wound repair after injury.Forty-eight full-thickness skin wounds were produced on both sides of the back in 6 male minipigs (8 wounds in each animal). Then these wounds were randomly divided into 4 groups, which were saline control group, fat autografting group, basic fibroblast growth factor (bFGF) treatment group and epidermal growth factor (EGF) treatment group. At day 3, 7, 14 and 21 after wounding, the area and the volume of wounds were measured and the histological examination was performed to evaluate the velocity and quality of wounds healing in different groups.At day 3 and 7, the amount of granulation tissues and vessel density in fat treatment group were significantly more than that in other groups. Wound areas and volume in fat treatment wounds were markedly decreased in compared with those in other groups (P 〈 0.01). Regenerated epidermis in fat treatment group was thicker than that in other groups.These results confirmed that the wound healing velocity and quality in wounds treated with fat autografting were enhanced. It indicated that fat has a potential to accelerate velocity and improve the quality of wound healing after skin injury.

Notizen: To explore the effects of bone marrow mesenchymal stem cells (MSCs) on the quality healing of porcine skin wounds after burn injury so as to provide a new method for clinical skin repair in the future. Seventy-two deep-partial thickness burn wounds were produced on the back of 6 minipigs and randomly divided into 6 groups: saline control, MSCs treatment, MSCs plus bFGF treatment, MSCs plus EGF treatment, bFGF treatment or EGF treatment only. MSCs were isolated from porcine marrow and cultured in vitro. After labeling with BrdU, MSCs were autografted onto the skin wounds. At 7, 14, 21 and 42 days after injury, the area of the wounds were measured and the histological examination was performed to evaluate the velocity and quality of wound healing. At 1, 2 and 4 weeks after transplantation, immunohistochemical examinations were carried out to detect the positive staining of BrdU, cytokeratin and S-100 to evaluate the wound healing quality. The area of wounds was decreased at day 7 and most of these wounds were healed on day 21 after injury. There was no significant difference on the contraction rate among six groups. Histological examination demonstrated that the number of vessel and the expression density of S-100 in MSCs plus bFGF treatment wounds were significantly enhanced than that in other groups. MSCs autografting may benefit to enhance the wound healing quality in porcine skin, which may open a new way to reach a “perfect repair” after skin injury.

Notizen: Polyclonal antibodies directed against human recombinant basic fibroblast growth factor were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. According to the intensity of the stain, three main classes of fibers could be identified: the strongly, moderately, and weakly stained fibers. Basic fibroblast growth factor immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, which includes the heparin-containing basal lamina, and also in the capillary basal membrane of both normal and wounded muscles; however, the signal intensity was much stronger in normal muscles. The distribution of basic fibroblast growth factor in wounded muscles became markedly heterogeneous and sparse. After 4 hours of ischemia, about 40% of skeletal muscle fibers lost their basic fibroblast growth factor immuno-reactivity. Muscles which underwent 4 hours of ischemia and 24 hours of reperfusion had only a diminished basic fibroblast growth factor immunoreactivity. The pathologic results supported the concept of destroyed cell connection and fiber necrosis in ischemic and reperfused muscles. Potential mechanisms involved in this reduced concentration of basic fibroblast growth factor in wounded muscles may include oxygen free radical activation, a generalized effect of the inflammatory response, and reduced secretion of endogenous basic fibroblast growth factor. These results are only partially compatible with the established mitogenic role of this growth factor and suggest that a reduction of endogenous fibroblast growth factor may partly contribute to a delay in wound healing.

Notizen: Fetal cutaneous wounds that occur in early gestation heal without scar formation. Although much work has been done to characterize the role of transforming growth factor-β (TGF-β) isoforms and their receptors in the wound healing process, their roles in scarless wound repair observed in early gestation and their functions in human fetal skin development, and structural and functional maintenance are still not well understood. In this study, we explore the expression and distribution characteristics of three TGF-β isoforms and their receptors, TGF-βRI (TBRI) and TGF-βRII (TBRII), in fetal and postnatal skins to understand the relevance of these five proteins to skin development and elucidate the mechanism(s) underlying the phenotypic transition from scarless to scar-forming healing observed during fetal gestation. Fetal skin biopsies of human embryo were obtained from spontaneous abortions at different gestational ages from 13 to 32 weeks and postnatal skin specimens were collected from patients undergoing plastic surgery. Gene expression and positive immunohistochemical signals of TGF-β1, TGF-β2, TGF-β3, TBRI, and TBRII could all be detected in fetal and postnatal skins. In early gestation, gene expression of TGF-β1, TBRI, and TBRII was weaker and protein contents were less compared with postnatal skins (p 〈 0.05). In contrast, more TGF-β2 mRNA transcript was found in early gestation than in late gestation and in postnatal skins, whereas protein content of this growth factor increased during gestation. Lastly, mRNA transcript and protein contents of TGF-β3 were apparently higher in early gestation compared to postnatal skin (p 〈 0.05). In postnatal skin, granules containing the three TGF-β isoforms were mainly distributed in the cytoplasm and extracellular matrix of epidermal cells, interfollicular keratinocytes, and some fibroblasts. TBRI and TBRII were chiefly located in the cellular membrane of epidermal keratinocytes and some fibroblasts. The endogenous three TGF-β isoforms and their receptors may be involved in the development of embryonic skin and in the maintenance of cutaneous structure and function, and also in postnatal wound healing. The differential levels of TGF-β isoforms may provide either a predominantly antiscarring or profibrotic signal upon wounding depending on the gestational period. Lower expression of their receptors in early gestational skins may be a reason for the reduced ability to perceive ligands, ultimately leading to scar-free healing.

Notizen: The development of sweat glands is a complex biological process, and the extent of cellular trafficking between epidermal stem cells and the development of sweat glands is uncertain. Therefore, we studied the synergetic development effects of stem cells, sweat glands, growth factors, and matrix metalloproteinases (MMPs) in human skin. Human fetal skin was obtained from spontaneously aborted fetuses at 11–31 weeks of gestation. Paraffin sections were cut and stained with hematoxylin and eosin or immunostained with antibodies against β1 integrin, keratin (K)-19 and K7, MMP-2 and -7, and epidermal growth factor. In situ hybridization was used along with semiquantitative analysis of the positive expression of these proteins to analyze for mRNA expression of MMP-2 and -7. Histological studies revealed the fetal epidermis began to form a primary epidermal ridge at gestational age 13–14 weeks and these primordial basal cells became tightly packed to take the form of multiple hillocks between 14 and 16 weeks. Furthermore, these cells gave rise to chord-like columnar buds in the embryonic epidermis, and these buds gradually migrated downward into the dermis to form juvenile sweat glands at 18–20 weeks. Mature sweat glands were found in the fetal epidermis at the end of 24 weeks. β1 integrin and K19 immunoreactivities were first detected in those cells that gathered together to form primary epidermal ridges, including sweat gland cords, buds, and immature sweat gland cells. The positive immunostaining for K7 appeared in early sweat gland buds at 14–16 weeks, and from then on K7 was concentrated in developing sweat gland cords or cells. At 14–16 weeks, positive epidermal growth factor, MMP-2, and MMP-7 expression was first observed weakly in developing sweat gland buds. The immunoreactivity of these proteins was then gradually increased in the developing sweat gland buds and extracellular stroma from 14 to 20 weeks. The intensity of the positive signal peaked at 20–22 weeks of gestational age. After that, the intensity of immunostaining for MMP-2 and MMP-7 proteins was gradually weakened. However, the expression of epidermal growth factor did not show an apparent decrease. These results suggest that epidermal stem cells are the source of sweat glands. Epidermal growth factor is one of the main inducers in the development and maturity of sweat gland buds or cells and the local activated MMPs may play an important role in cleaving the major matrix components in the basement membrane.

Notizen: Adult stem cells are found in various tissues and organs and have potential to differentiate into different cell lineages, including bone, cartilage, fat, tendon, muscle, epithelial cells of the skin and gastrointestinal tract, etc. Here, we report that the expended and purified bone marrow MSCs might take on phenotypes and characteristics of vascular endothelial cells or epidermal cells after cultured and induced with different lineage-specific culture conditions in vitro. Also, in vivo grafting experiments confirmed that those labeled MSCs could get the phenotypes of vascular endothelial cells in granulation tissue and sebaceous duct cells and epidermal cells in regenerated skin, which imply that these grafted MSCs might have transdifferentiated into vascular endothelial cells and sebaceous duct cells and epidermal cells. Our results indicate that locally delivered bone marrow MSCs may generate de novo intact skin and get perfect skin regeneration after full thickness injury.

Notizen: In the past 10 years, many engineered growth factors, including recombinant human epidermal growth factor, basic fibroblast growth factor, and platelet-derived growth factor, have been produced and used in the clinic. After screening the results from different centers, some results are found to be encouraging, while others are discouraging. Although the interpretation of these results may depend on your perspective, it may also depend on different criteria, different wounds, and even different aims. In this article, successful experiences and failures concerning the use of growth factors and cutaneous wound healing are summarized. Based on this information and our clinical experience, we address people's concerns such as whether growth factors have altered clinical practice thus far and whether growth factor treatments have solved all problems involved in wound healing. Is there a need for exogenous application of growth factors in acute or chronic wounds, and if so, is it safe to use growth factors to promote wound healing? Last, can we achieve perfect wound healing in those wounds treated with growth factors?

Notizen: China is the largest developing country in the world with wounds occuring everyday and everywhere, representing one of the main killers of people. Prevention and treatment of wounds are the main tasks for Chinese surgeons. Although wound care and management have a long history in China, wound healing research and management have made significant progress only in recent years. In this article we give a brief account of the history of wound care and management in China. In addition, we introduce the main research fields and achievements in tissue repair and regeneration during recent times in this country. We hope that these works will benefit our foreign colleagues to know our work and enhance the communication among us.

Notizen: A total of 30,000 hospitalized surgical patients in 15 hospitals were screened for chronic ulcers. A total of 489 patients with chronic dermal ulcers were found with their major causes of ulceration including traumatic wounds, infections, diabetes mellitus, and venous diseases. Patients with chronic ulcers following trauma and infection comprised 67.48% of the total patient population. The incidence of diabetic ulcers and venous ulcers was 4.91% and 6.54% respectively. Sites of ulceration differed with different etiological factors. The percentage of chronic dermal ulcers in the lower extremities, upper extremities, thorax and abdomen, back, and head was 63.10%, 17.93%, 7.76%, 4.83% and 6.38% respectively. Of the 489 patients with chronic ulcers, 183 were farmers (37.42%), and 131 were workers (26.79%). Chronic dermal ulcers were more common in men than in women, but there was no significant difference in the sex-related prevalence. According to these data from different hospitals, the incidence of chronic ulcers in patients hospitalized for surgery was 1.5% to 3.0%. These data have primarily shown the prevalence and clinical characteristics of chronic ulcers in hospitalized patients in China. These data may not be consistent with reports from other countries. Significant differences in etiological factors of ulceration, professional distribution of patients with chronic dermal ulcers, and treatment methods were found when compared with reports of studies conducted in developed countries. Our results will benefit not only additional basic research, but these data will also be useful in preventing and managing chronic wounds in developing countries.