Effect of Fibroblasts on Tracheal Epithelial Regenerationin vitro

Abstract

Several artificial grafts for covering deficient trachea have been produced through tissue engineering. Recently, our group clinically used an artificial trachea made from collagen sponge for patients with noncircumferential tracheal resection. However, the slowness of epithelial regeneration on the surface of the artificial trachea was confirmed as one particular problem. In this study, we co-cultured tracheal epithelial cells with fibroblasts and examined effects of fibroblasts on epithelial regeneration in vitro. Fibroblasts activated epithelial cell proliferation and migration. In co-culture with fibroblasts, epithelial cells reconstructed pseudostratified epithelium, which was composed of ciliated, goblet, and basal cells. Furthermore, a basement membrane was reconstructed between epithelial cells and fibroblasts, and integrin beta4 was also observed there. Fibroblasts rapidly increased mucin secretion by epithelial cells. These results indicate that stimulatory effects of fibroblasts on epithelial cell migration, proliferation, and differentiation would reduce the time required for covering of epithelial cells on the defect of luminal surface and hasten regeneration of morphologically and functionally normalized epithelium involving the reconstruction of basement membrane.

Effect of Structural Differences in Collagen Sponge Scaffolds on Tracheal Epithelium Regeneration

“…20.21 Indeed, our group has previously shown that stratification, basement membrane reconstruction, apicobasal polarization, and cilia formation of cultured tracheal epithelial cells were promoted by co-culture with fibroblasts. 10 Moreover, following study has indicated that mesenchymal cells stimulate growth and the differentiation of tracheal epithelial cells during tracheal regeneration in a rat tracheal defect model. 22 Thus, mesenchymal cell invasion is an essential event for epithelial regeneration.…”

“…7 To promote regeneration of the tracheal epithelium, our group has studied the effects of fibroblasts, adipose-derived stem cells, and basic-fibroblast growth factor in artificial grafts and shown that they shorten the time for epithelialization and cilia formation. [8][9][10][11][12][13][14] Collagen scaffolds are widely used in regenerative medicine because of their high biocompatibility, but no studies have examined the most suitable structure of collagen scaffold for tracheal regeneration.…”

A scaffold-bioreactor system for a tissue-engineered trachea

“…In addition, techniques such as co-culture of two types of cells (i.e. epithelia and fibroblasts) [38] or transplant of the tracheal epithelial cell sheets can be employed to reduce airway stenosis [39]. Overall, for the reconstruction of large segment tracheal defects, the intact epithelial lining is essential to prevent bacterial colonization or infection.…”

Regenerative Medicine: Reconstruction of Tracheal and Pharyngeal Mucosal Defects in Head and Neck Surgery

“…They are able to secrete a variety of growth factors like keratinocyte growth factor, epidermal growth factor, and hepatocyte growth factor [92,93] . The importance of fi broblasts was shown already for epidermal wound healing [93] , oral [94] and corneal epithelial regeneration [95] , and also for tracheal epithelial regeneration [96] . The cocultivation of epithelial cells and tracheal fi broblasts in vitro induced the generation of a layered epithelium containing epithelial cells with cilia, goblet cells, and basal cells.…”

“…The cocultivation of epithelial cells and tracheal fi broblasts in vitro induced the generation of a layered epithelium containing epithelial cells with cilia, goblet cells, and basal cells. Moreover, a basal membrane was constituted in vitro between epithelial cells and fi broblasts where the presence of integrin -β 4 was demonstrated, which is a specifi c marker of basal membranes and of epithelial mucin secretion [96] .…”