Fibroblast differentiation of bone marrow-derived cells during wound repair.

To examine the ontogeny of the wound fibroblast, bone marrow transplantation was performed to wild-type recipients from transgenic donors that express both the luciferase and beta-galactosidase reporter genes under transcriptional control of the promoter/enhancer for the alpha2 chain of type I collagen. Polyvinyl alcohol sponges were implanted to elicit a naïve granulation tissue response, removed at defined time points, and processed for nucleic acids and histochemistry. Quantitative PCR for the luciferase transgene demonstrated that donor-derived cells were present during inflammation, declined, and rebounded during later stages of tissue remodeling. Furthermore, quantitative RT-PCR revealed that bone marrow-derived collagen transcripts contributed significantly to the total collagen I alpha2 promoter activation during later stages of repair. beta-galactosidase staining revealed that indeed those cells which expressed the transgene exhibited a fibroblastic phenotype, co-localized with sites of active collagen deposition, and expressed fibroblast specific protein-1. These data strongly support the concept that the adult bone marrow compartment houses progenitors with the potential to migrate to sites of tissue damage, and participate in repair beyond inflammation as fibroblasts. Moreover, that bone marrow-derived fibroblasts make a substantial contribution to the formation of new connective tissue, including type I collagen, during wound repair.