In vitro formation of fibrous septa by liver connective tissue cells

Active fibrous septa are a common feature in liver fibrosis and cirrhosis. Their etiology and formation were studied using cultures of tissue fragments or cells included in collagen gels. Liver fragments obtained from patients with cirrhosis or severe schistosomal fibrosis were able to reorganize the gel and to form discrete, interconnecting fibrous septa composed of parallel arrays of collagen, subsequently colonized by migrating connective tissue cells. The same was obtained in cultures of fibrogranulomatous lesions isolated from schistosome-infected mice livers. However, fragments of normal human and murine liver tissue did not show the capacity to form fibrous septa. Septa formation was also obtained in cultures of cell spheroids formed by liver connective tissue cells isolated from human fibrotic or cirrhotic liver tissues, but not with spheroids of normal skin fibroblasts or smooth muscle cells. This experimental model may represent the fibrous septa formation in vivo, depending on the activity of liver connective tissue cells. The ability of tissue fragments or cell spheroids to form septa in collagen gels might reflect the degree of fibrosis present in the liver tissue in vivo.