Our current technique of in situ tissue engineering using a scaffold shows great potential for use in the regeneration of airway defects.

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These results suggested that implanted ASCs accelerated neovascularization and epithelialization on the regenerated trachea. Thus, our newly developed bioengineered scaffold contributes to tracheal regeneration.

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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.

SV atrophy appears to be the most prominent anatomic characteristic of aged human cochleae.

The tracheal epithelium maintains the health of the respiratory tract through mucociliary clearance and regulation of ion and water balance. When the trachea is surgically removed, artificial grafts have been clinically used by our group to regenerate the trachea. In such cases, the tracheal epithelium needs 2 months for functional regeneration. Previous study has shown that fibroblasts facilitate tracheal epithelial regeneration. In this study, heterotopic fibroblasts originating from the dermis, nasal, and gingival mucosa were cocultured with tracheal epithelial cells to evaluate their potential as autologous transplanted cells for tracheal epithelial regeneration. The epithelia induced by the heterotopic fibroblasts showed differences in structure, cilia development, mucin secretion, and expression of ion and water channels. These results indicated that nasal fibroblasts could not induce mature tracheal epithelium and that dermal fibroblasts induced epidermis-like epithelium. Only the gingival fibroblasts (GFBs) could induce morphologically and functionally normalized tracheal epithelium comparable to the epithelium induced by tracheal fibroblasts. Epithelial cell proliferation and migration were also upregulated by GFBs. These results indicate that GFBs are useful as autologous transplant cells for tracheal epithelial regeneration.

Our technique for trachea reconstruction using a novel bipotential collagen scaffold affords a feasible approach for accelerating epithelial regeneration on the intraluminal surface of the host tracheal defect.