Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic.

BACKGROUND: While several commercial dermoepidermal scaffolds can promote wound healing of the skin, the achievement of complete skin regeneration still represents a major challenge. OBJECTIVES: To perform biological characterization of self-assembled extracellular matrices (ECMs) from three different subpopulations of fibroblasts found in human skin: papillary fibroblasts (Pfi), reticular fibroblasts (Rfi) and dermal papilla fibroblasts (DPfi). METHODS: Fibroblast subpopulations were cultured with ascorbic acid to promote cell-assembled matrix production for 10 days. Subsequently, cells were removed and the remaining matrices characterized. Additionally, in another experiment, keratinocytes were seeded on the top of cell-depleted ECMs to generate epidermal-only skin constructs. RESULTS: We found that the ECM self-assembled by Pfi exhibited randomly oriented fibres associated with the highest interfibrillar space, reflecting ECM characteristics that are physiologically present within the papillary dermis. Mass spectrometry followed by validation with immunofluorescence analysis showed that thrombospondin 1 is preferentially expressed within the DPfi-derived matrix. Moreover, we observed that epidermal constructs grown on DPfi or Pfi matrices exhibited normal basement membrane formation, whereas Rfi matrices were unable to support membrane formation. CONCLUSIONS: We argue that inspiration can be taken from these different ECMs, to improve the design of therapeutic biomaterials in skin engineering applications.

Carcinoma of sigmoid colon after ureterosigmoidostomy.

An unusual case of adenocarcinoma of the colon in a 49-year-old man is described. The patient underwent ureterosigmoidostomy at the age of 3 years after a traffic accident. At the age of 49 years, he was admitted to a Department of Urology for treating urinary lithiasis. A chest x-ray and thoracic computed tomography (CT) showed some nodules in both pulmonary fields, while an abdominal CT was normal. The previous patient's history was ignored, the patient underwent thoracoctomy and a nodule was removed. The histology revealed a metastatic, moderately differentiated mucinous adenocarcinoma, probably of the bowel. A sunsequent colonoscopy was non-disclosing and the patient was thought to suffer from a carcinoma of unknown origin and received 6 cycles of chemotherapy with carboplatin and 5-fluorouracil. Five months after the end of chemotherapy he presented with an uncerated mass in the lower abdominal wall. A new CT scan revealed a solid mass in the pelvis with infiltration of the suprapubic region while a repeat colonoscopy showed an infiltrating mass in the sigmoid. Biopsies were obtained from both lesions and the histology was similar with that of the pulmonary nodule.