Hiding in Plain Sight: Human Gingival Fibroblasts as an Essential, Yet Overlooked, Tool in Regenerative Medicine

Adult human gingival fibroblasts (HGFs), the most abundant cells in the oral cavity, are essential for maintaining oral homeostasis. Compared with other tissues, adult oral mucosal wounds heal regeneratively, without scarring. Relative to fibroblasts from other locations, HGFs are relatively refractory to myofibroblast differentiation, immunomodulatory, highly regenerative, readily obtained via minimally invasive procedures, easily and rapidly expanded in vitro, and highly responsive to growth factors and cytokines. Consequently, HGFs might be a superior, yet perhaps underappreciated, source of adult mesenchymal progenitor cells to use in tissue engineering and regeneration applications, including the treatment of fibrotic auto-immune connective tissue diseases such as scleroderma. Herein, we highlight in vitro and translational studies that have investigated the regenerative and differentiation potential of HGFs, with the objective of outlining current limitations and inspiring future research that could facilitate translating the regenerative potential of HGFs into the clinic.

Automated summary

Adult human gingival fibroblasts (HGFs) are important for maintaining oral homeostasis and have great potential for tissue engineering and regeneration applications. They have unique characteristics such as resistance to myofibroblast differentiation, immunomodulation, high regenerative capacity, and responsiveness to growth factors and cytokines. This review highlights in vitro and translational studies on the regenerative and differentiation potential of HGFs and emphasizes the need for further research to translate their potential into clinical applications.