Porcine small intestinal submucosa (SIS): a bioscaffold supporting in vitro primary human epidermal cell differentiation and synthesis of basement membrane proteins

The growth pattern of human epidermal cells, fibroblasts or Swiss mouse 3T3 /J2 fibroblasts cultured upon the extracellular matrix (ECM) derived from s mall intestinal submucosa (SIS) was evaluated. The cell/SIS composites were grown submerged, then maintained in air/liquid interface for 2, 7, 10 or 1 4 days. The presence of differentiation-related keratins 10, 14 and 16, FN, laminin, collagen type VII and collagen type IV was determined by immunohi stochemical methods in SIS alone and in the SIS/cell composite. Only FN cou ld be detected in SIS alone. SIS supported the formation of an epithelial s tructure with suprabasal expression of K16 and regional suprabasal expressi on of K10. The epidermal cells were K14 positive and tended to 'invade' the SIS to various degrees. Following the growth of epidermal cells and fibrob lasts on the SIS substratum, immunolabeling of FN, laminin, collagen type V IT and collagen type IV was observed in a cell-associated pattern. The fibr oblasts commonly invaded the SIS, when co-cultivated with epidermal cells o n the opposite side of the SIS. The ability of SIS to support epidermal cel l/fibroblast attachment, migration and/or proliferation and differentiation with deposition of basement membrane (BM) components indicates that the co mposite model may be useful for studying cell-matrix interactions and for i nvestigation as a dermal substitute. (C) 2001 Elsevier Science Ltd and ISBI . All rights reserved.