Differential behavior of fetal and adult fibroblasts: Implications for regenerative tissue healing.

摘要

The high incidence of tendon injuries in the United States has resulted in novel experimental approaches to engineer cell-based analogs as alternatives to autologous and allogeneic tissue grafts. The source of cells can have a significant impact on the development of such constructs. Given the known regenerative properties of fetal tissues, the objectives of this thesis research were to (1) evaluate the differences between fetal and adult fibroblasts in two- and three-dimensional culture and to; (2) harness the regenerative capacity of fetal skin and tendon cells to engineer three-dimensional composites for tendon wound healing applications. Fetal and adult tendon and dermal fibroblasts were isolated from pregnant sheep and rats and their fetuses and evaluated in monolayer and three-dimensional culture for migration, adhesion, growth, and extracellular matrix elaboration. Fetal dermal fibroblasts displayed serum-independent adhesion and growth, despite serum-dependent migration in monolayer culture. In addition, fetal dermal fibroblasts elaborated more type I collagen compared to adult dermal fibroblasts. Also, fetal tendon fibroblasts were shown to exhibit increased migration and collagen production compared to adult tendon fibroblasts in two-dimensional culture. Similar properties were found for three-dimensional analogs. Specifically, fetal tendon fibroblast-seeded constructs elaborated significantly more collagen compared to adult specimens; and fetal dermal fibroblasts displayed enhanced proliferation, total protein, and type I collagen production compared to adult dermal fibroblasts seeded on three-dimensional polymer scaffolds. Additionally, fetal dermal constructs exhibited increased mechanical properties when compared to adult samples. Taken together, these findings suggest that fetal fibroblasts are intrinsically different from adult fibroblasts. Furthermore, fetal fibroblasts possess properties (i.e., enhanced adhesion, growth, migration, and collagen production) that may give rise to the regenerative wound healing process observed in fetal skin and tendons. Building on the knowledge gained by this thesis research, it may be advantageous for investigators to use fetal fibroblast-seeded constructs for tendon wound healing applications. In addition, by discerning the differences between fetal and adult fibroblasts, it may be possible to develop alternative therapies for improving adult tendon repair.