Bone marrow-derived myofibroblasts recruited to the upper dermis appear beneath regenerating epidermis after deep...

Fibroblasts and myofibroblasts migrating to sites of tissue repair after injury may not only be locally recruited but could also be recruited from the bone marrow. However, the characteristics and functional roles, if any, of these cells in wound healing are poorly understood. Here, we show unequivocally that bone marrow-derived fibroblasts do contribute to deep dermal burn wound healing. Bone-marrow stromal cells were collected from femurs of male Lewis rats, cultured for a week, and then the adherent cells were labeled with the fluorescent marker PKH-26. These cells stained positive for alpha-smooth muscle actin and prolyl 4-hydroxylase, but did not express RM-4 (a macrophage marker), CD34, or cytokeratin, characteristic of myofibroblastic differentiation. When injected intravenously into Lewis rats, they homed to the bone marrow. Five days after transplantation, a deep dermal burn was made on the back of the rat, and biopsies were taken 7, 10, and 14 days later. PKH-positive cells were not found at day 7, but by day 10, they were easily detected mainly in the upper dermis close beneath the regenerating epidermis. These PKH-positive cells still stained for alpha-SMA and prolyl 4-hydroxylase, but not RM4. Thus, it is suggested that myofibroblasts originating in the bone marrow contribute not only to promotion of granulation but also enhancement of dermal-epidermal interaction after thermal injury.