Department of Organ Regulation Medicine

Plastic Surgery

Surgical techniques that restore morphology and function without scarring
  • Surgical treatments with minimal scarring
  • New regenerative medicine to treat peripheral nerve injury using adipose-derived stem cells
  • Elucidation of the mechanisms for peripheral nerve regeneration
  • Developing new methods to treat facial nerve paralysis
Professor Tateki KUBO
Graduate School of Medicine, Department of Plastic Surgery
The origins of this department date back to 1980, when the plastic surgery group was formed as a part of the dermatology department. Initially, the group was headed by Koreaki Matsumoto, who was later succeeded by Ko Hosokawa. The plastic surgery group became its own department in 1999, and Hosokawa was appointed its first professor. In 2019, Tateki Kubo assumed the role of second, and current department professor.

Using unique techniques such as microsurgery, we aim to restore morphology and function. We strive for originality in research.

Our laboratory conducts research on wound healing with the aim of making medical treatments that leave no scarring. We also study the mechanisms that promote peripheral nerve regeneration, as well as adipose tissue-derived stem cells.

Fibroblasts and myofibroblasts play key roles in healing wounds in the skin. Our studies focus on the cytoskeleton regulation of such cells, with a focus on factors including RhoA, Rac1, and Cdc42. In our previous work, we discovered that the administration of bFGF to fibroblasts improves wound healing, as it activates Rac1 to promote lamellipodia formation and fibroblast migration. We also determined that the signal transduction from PI3-kinase through Rac1 to JNK. Furthermore, we found that endothelin-1, a vascular endothelial-derived factor, activates RhoA in fibroblasts and induces myofibroblast differentiation, which promotes the formation of abnormal scars like keloids and hypertrophic scars (see illustration).

 

Figure
Endothelial cells in abnormal scar secret endothelin-1. Then, endothelial cell-derived endothelin-1 affects dermal fibroblasts and activates the RhoA/Rho-kinase pathway through the endothelin receptor, which results in myofibroblast differentiation, collagen synthesis, upregulation of contractile properties, and abnormal scar formation.

Facial paralysis is an intractable disorder often encountered in the field of plastic surgery. For the development of novel therapeutic treatments, we focused on similar factors related to wound healing such as RhoA, Rac1 and Cdc42, and clarified the mechanism of axon extension promotion in peripheral nerves. We identified that inhibition of RhoA promotes recovery after motor nerve injury. We are currently also working towards the development of new regenerative medicine for peripheral nerve injury using adipose tissue-derived mesenchymal stem cells.

Furthermore, we developed an innovative model of co-culturing skin fibroblasts and neurons to study the interaction between skin and nerve, which are two seemingly different systems. Using this model, we discovered that upon with neurites, differentiation of fibroblasts into myofibroblasts is being promoted hence enhancing wound contraction.

We will continue to further explore the mechanisms behind the above findings, with the aim to ultimately achieve scarless wound healing in medical treatments and full regeneration of peripheral nerve damage.

Facial paralysis is a frequent but undesirable peripheral neuropathic outcome of plastic surgery. To develop new methods of treatment for this condition, as with the wound-healing, we again are focusing on factors such as RhoA, Rac1, and Cdc42, in order to determine the mechanism that encourages axonal development in the peripheral nerves. In doing so, we found that the inhibition of RhoA results in accelerated recovery following injury to motor nerves. We are also currently working to develop new regenerative medicine to treat peripheral nerve injuries using adipose tissue-derived stem cells. Our laboratory is also conducting unique research that combines the aforementioned studies of the skin and nerves. To do so we have developed a new model, in which we culture skin fibroblasts together with neurons. Using this model, we discovered that with neurites promotes the differentiation of fibroblasts into myofibroblasts, accelerating wound contraction. We plan to continue to investigate these findings as we continue to work towards our goals of making scar-less medical treatment a reality, and towards achieving full regeneration of damaged peripheral nerves.