Published papers

In fetal regenerative wound healing, dermal mesenchymal cells directly migrate into the wound and regenerate the dermal structure. On the contrary, loose fascial cells beneath the dermis construct scar tissue in the late stage of development. We co-transplanted fetal epidermal cells and dermal or loose fascial mesenchymal cells onto a skin defect in SCID mice to evaluate the regenerative activity of their skin. The cells used for transplantation were obtained from fetal C57b1 mice on embryonic day 17, and suspended enzymatically. Four weeks after the transplantation, almost normal skin was regenerated in the animals that were transplanted with dermal and epidermal cells. Conversely, scar-like tissue was constructed in the animal wounds into which loose fascial and epidermal cells were transplanted. We found it useful to use this model to evaluate the cutaneous regenerative activity of various cells.

Vascular systems of the flaps are constructed of following elements; i) types of blood circulation in the flaps, ii) vessel types of vascular pedicles, iii) separation points of vascular pedicles. The blood circulation of flaps is constructed of the dermal vascular system and the subdermal vascular system. Based on the combination of these elements, skin flaps can be categorized into the thin cutaneous flap, the split thickness cutaneous flap, and the full thickness cutaneous flap. The blood circulation in the deep fascia itself is poor, and thus the deep fascia does not contribute to the blood supply of the cutaneous flaps. Accordingly, the cutaneous flaps containing the whole subcutaneous adipose layer without deep fascia is basically similar to the fasciocutaneous flap. However, we categorized the former as full thickness cutaneous flap to prevent the confusion of terminology. From the clinical aspects, perforating vessels that construct the vascular pedicles were categorized into 6 types based on the vascular pattern from the source vessel to the dermal plexus. These six types of perforating vessels can be simplified as follows: 1) direct cutaneous vessels, 2) accompanying vessels, 3) muscular artery perforators, 4) septal perforators.

Background: The platysma flap has often been used for reconstructions of the head and neck, but the arterial anatomy of the platysma itself has not been clarified. Methods: The anterolateral neck skin in five sides of four fresh cadavers that had been injected systemically with a lead oxide-gelatin mixture was elevated and divided into three layers: the skin with adipofascial tissue over the platysma, the platysma, and the adipofascial tissue under the platysma. Radiographs were taken of each specimen using the soft x-ray system. Results: The anterolateral neck skin was chiefly supplied by branches of the submental, facial, superior thyroid, transverse cervical, and occipital arteries, and it was found that the vasculature of the arterial branches can be classified into three groups. In all of the groups, the arterial branches penetrated the platysma and did not run long in the platysma layer. The platysma was supplied by only small vessels from the arterial branches. Furthermore, there was little connection between the vascular plexus of the platysma and that of the skin layer with adipofascial tissue above the platysma and the platysma located in the subcutaneous tissue. Conclusions: The platysma flap should be considered fasciocutaneous rather than musculocutaneous. Therefore, the platysma flap should usually be elevated with the deep adipofascial tissue under the platysma. Flap survival is threatened if it is elevated without the adipofascial tissue under the muscle as with a usual musculocutaneous flap.

Mesenchymal stem cells (MSCs) possess the capacity for site-specific differentiation of cell types in response to cues provided by different organs. This phenomenon suggests that MSCs participate in cutaneous wound regeneration. However, there are no prior reports on the influence of the local application of MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound regeneration, we cultured bone marrow cells of the femur of rats and treated the plastic adherent cells with a differentiation medium to induce differentiation. After treatment, we found that the bone marrow-derived plastic adherent cells possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating that these cells are MSCs. The bone marrow-derived plastic adherent cells were injected intradermally into the skin of rats, and linear full-thickness incisional wounds were made immediately through the injected area. At 14 days after operation, wounds transplanted with bone marrow-derived plastic adherent cells had healed with very fine scars. Collagen architecture was thick and appeared to be similar to normal dermis. Histomorphologic scale analysis demonstrated significant differences between the control and the wounds transplanted with bone marrow-derived plastic adherent cells. These results indicate that transplanted MSCs can respond quite normally to wound healing and regenerate dermal structure.

The subcutaneous adipofascial tissue over the entire body was radiographically and macroscopically investigated in 20 fresh and embalmed cadavers. The subcutaneous adipofascial tissue was made up of two adipofascial layers. Because the superficial layer forms a solid structure and is thought to protect against external forces, the adipofascial system formed by the solid structure was named the "protective adipofascial system (PAFS)". Because the deep layer forms a mobile layer and is thought to lubricate musculoskeletal movement, the adipofascial system formed by the mobile structure was named "lubricant adipofascial system (LAFS)". By classifying subcutaneous adipofascial tissue by its functional characteristics, we found we could understand the subcutaneous adipofascial structure over the entire body well.

Skin fibroblast cultures were established from mouse foetuses at days 14, 15, 16 and 18 of gestation and from newborn mice. Modulations of mitotic and biosynthetic phenotypes of the fibroblasts by transforming growth factor β1 (TGFβ1) were studied. Treatment of the fibroblasts with TGFβ1 at doses of 1 and 10 ng/ml for 48 h resulted in significant stimulation of cell proliferation in the 15-, 16- and 18-day foetal fibroblasts and a slight stimulation in the 14-day foetal fibroblasts. Treatment with TGFβ1 resulted in stimulation of collagen synthesis approximately 2-fold in the 18-day foetal and newborn fibroblasts, but failed to stimulate it in the 14-, 15- and 16-day foetal fibroblasts. TGFβ1 stimulated glycosaminoglycan (GAG) synthesis throughout all developmental stages approximately 1.8-2.6 fold. Histological study demonstrated that skin wounds made at day 16 of gestation were replaced with normal-appearing dermis, but at day 18 the wounds left dermal fibrosis and lack of hair follicles. These results indicate that the modulations of fibroblast phenotypes (proliferation and syntheses of collagen and GAG) in response to TGFβ1 occur at different stages of gestation. Ontogenic transitions of skin wound healing and collagen synthetic phenotype with TGFβ1 treatment in cultured fibroblasts occurred between days 16 and 18 of gestation, suggesting that the unresponsiveness of collagen synthesis to exogenous TGFβ1 in cell culture may be related to the phenomenon of scarless wounds in the foetus.