CLINICAL APPLICATION OF EX VIVO PRODUCED ORAL MUCOSA EQUIVALENT

Abstract

Recently, some grafting techniques utilizing cultured keratinocytes are widely used to treat various skin wounds. However, fetal calf serum (FCS) is indispensable for their optimal growth in these culture methods. FCS may carry the risk of transmitting infectious agents such as prions and unknown viruses, although there has been no report on the development of such infectious diseases after grafting cultured keratinocytes. When feeder layer cells, irradiated to render them nonproliferative, such as 3T3 mouse cells are utilized for the culture of keratinocytes, the grafted procedures should be detined as xenotransplantation under the FDA in the U.S. and Ministry of Health, Labour and Welfare in Japan. We never use any serum or animal cells to culture keratinocytes, and obtained a stratified squamous epithelium which histologically resembled the in vivo original structures of normal epithelium, using an acellular dermis (AlloDerm^®) as a scaffold. In these basic researches, we tried using the ex vivo produced oral mucosa equivalent in a total of 106 cases of clinical applications after gaining informed consent, supported by a Grant for the Development of Highly Advanced Medical Technology B from the Ministry of Education, Culture, Sports, Science, and Technology of Japan for three consecutive years from 2002 to 2004. As a result, 90 grafts clinically took well and became almost normal oral mucosa uneventfully. The advantages of our method are that our material is not regarded as a xenogeneic graft tissue because we avoid any risk of transmitting infections theoretically and that the surgeon can grasp the grafted equivalent with forceps and easily suture the wound bed with a tie-over technique. The disadvantages are that an acellular dermis from cadaveric skin is used to make a composite equivalent, and it takes about one month to produce it.