Human amniotic fluid derived cells can competently substitute dermal fibroblasts in a tissue-engineered dermo-epidermal skin analog

<p>Human amniotic fluid comprises cells with high differentiation capacity, thus representing a potential cell source for skin tissue engineering. In this experimental study, we investigated the ability of human amniotic fluid derived cells to substitute dermal fibroblasts and support epidermis formation and stratification in a humanized animal model.</p><p>Dermo-epidermal skin grafts with either amniocytes or with fibroblasts in the dermis were compared in a rat model. Full-thickness skin wounds on the back of immuno-incompetent rats were covered with skin grafts with (1) amniocytes in the dermis, (2) fibroblasts in the dermis, or, (3) acellular dermis. Grafts were excised 7 and 21 days post transplantation. Histology and immunofluorescence were performed to investigate epidermis formation, stratification, and expression of established skin markers.</p><p>The epidermis of skin grafts engineered with amniocytes showed near-normal anatomy, a continuous basal lamina, and a stratum corneum. Expression patterns for keratin 15, keratin 16, and Ki67 were similar to grafts with fibroblasts; keratin 1 expression was not yet fully established in all suprabasal cell layers, expression of keratin 19 was increased and not only restricted to the basal cell layer as seen in grafts with fibroblasts. In grafts with acellular dermis, keratinocytes did not survive.</p><p>Dermo-epidermal skin grafts with amniocytes show near-normal physiological behavior suggesting that amniocytes substitute fibroblast function to support the essential cross-talk between mesenchyme and epithelia needed for epidermal stratification. This novel finding has considerable implications regarding tissue engineering.</p>

Fetal bladder wall regeneration with a collagen biomatrix and histological evaluation of bladder exstrophy in a fetal sheep model.

Contains fulltext : 70288.pdf (publisher's version ) (Closed access)OBJECTIVES: To evaluate histological changes in an animal model for bladder exstrophy and fetal repair of the bladder defect with a molecular-defined dual-layer collagen biomatrix to induce fetal bladder wall regeneration. METHODS: In 12 fetal lambs the abdominal wall and bladder were opened by a midline incision at 79 days' gestation. In 6 of these lambs an uncorrected bladder exstrophy was created by suturing the edges of the opened bladder to the abdominal wall (group 1). The other 6 lambs served as a repair group, where a dual-layer collagen biomatrix was sutured into the bladder wall and the abdominal wall was closed (group 2). A caesarean section was performed at 140 days' gestation, followed by macroscopic and histological examination. RESULTS: Group 1 showed inflammatory and maturational changes in the mucosa, submucosa and detrusor muscle of all the bladders. In group 2, bladder regeneration was observed, with urothelial coverage, ingrowth of fibroblasts and smooth muscle cells, deposition of collagen, neovascularization and nerve fibre formation. This tissue replaced the collagen biomatrix. No structural changes of the bladder were seen in group 2. CONCLUSIONS: The animal model, as in group 1, for bladder exstrophy shows remarkable histological resemblance with the naturally occurring anomaly in humans. This model can be used to develop new methods to salvage or regenerate bladder tissue in bladder exstrophy patients. Fetal bladder wall regeneration with a collagen biomatrix is feasible in this model, resulting in renewed formation of urothelium, blood vessels, nerve fibres, ingrowth of smooth muscle cells and salvage of the native bladder