Inhibition and reversal of a TGF-ß1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors.

BACKGROUND: Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. METHODS: The transforming growth factor-ß1 (TGF-ß1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. RESULTS: Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-ß1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. CONCLUSIONS: Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism.

Pyogenic granuloma - the quest for optimum treatment: audit of treatment of 408 cases.

Pyogenic granuloma is a common, acquired, benign vascular lesion of skin and mucous membranes which may occasionally present intravascularly or subcutaneously. Pyogenic granuloma occur in all age groups and although they may eventually regress, removal of unsightly, bleeding or uncomfortably positioned lesions is usually sought before this takes place. This is a retrospective study of 408 cases of pyogenic granuloma that were analysed by the Stoke Mandeville Histopathology laboratory between 1994 and 2004. This study was carried out to review the sex, age and anatomic distribution of the lesions and to assess the most successful form of treatment on the basis of recurrence risk and other measures such as aesthetic result, acceptability and appropriateness of the procedure with respect to the patient. There was a slight male preponderance especially among children. The exception to this was lesions on mucous membranes, which were more common in women. Head and neck was the most common anatomical location, in particular the cheek and intraoral locations. Fewest recurrences were noted following excision and direct closure although all techniques investigated showed an acceptably low recurrence rate. Whatever technique is used it must yield material for histopathological analysis to ensure the exclusion of differential diagnoses.

Incidence, mortality and survival in cutaneous melanoma.

Cutaneous melanoma remains a challenge despite increased levels of awareness, education and targeted health policies. Worldwide incidence rates for cutaneous melanoma have risen faster than those for any other malignancy in Caucasian populations over the last 30 years. Despite improving survival rates (defined as the ratio of those who survive the disease against incidence) over this period, mortality rates, generally, have continued to climb. Mortality from melanoma is greater than that caused by all other types of skin cancer, especially in men. In Britain the percentage of increase in the male age standardised mortality rate surpassed that of all other malignancies assessed (1993-2002) by Cancer Research UK. A literature-based study was conducted with review of publications identified through Medline and EMBase, 1980-December 2005, databases. We present a review of the current literature on incidence, mortality and survival rates of melanoma including a discussion on the aetiological factors, behaviour modification associated with public education campaigns and recent health policies and the effect these are having on melanoma figures. It is likely that any fall in mortality rates from melanoma in the near future will be secondary to early detection. Changes resulting from primary prevention are unlikely to be noticeable for several decades.