YUJI YAMAGUCHI Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences

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1 Nagoya Med. J., 149 Current status of regenerative medicine through the treatment for intractable skin wounds YUJI YAMAGUCHI Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences Since skin is easy to handle, the clinical application of regenerative medicine including ips induced pluripotent stem cell therapy is quite realistic to treat various skin diseases in the very near future. In spite of the development of artificial skin equivalents for wide spread burn, the current status of skin regenerative medicine has a lot of issues to overcome in terms of the fragility to infection and the low acceptance rate of skin equivalent grafts. Here is the report about intractable skin wounds caused by diabetes mellitus, critical limb ischemia, rheumatism, collagen diseases and pressure sores that can be treated at any facility with healthcare services provided by health insurance. Wounds with exposed bones are aggressively debrided with a bone scraper, followed by the immediate coverage of occlusive dressing. This method is for providing bone marrow cells with niche to achieve the differentiation of skin cells. After healthy granulation tissue is observed, epidermal grafting, which is obtained from suction blister roofs, accomplishes the site-specific anatomically suitable differentiation of the grafted areas. Now this treatment option is widely recognized in dermatology field and is reported here since the concept of this therapy may be useful to apply for the other organs, aiming for the perfect tissue regeneration. 149

2 150 Gastrin releasing peptide Hepatocyte growth factor calciphylaxis calcific uremic arteriolopathy ips induced Pluripotent Stem MRSA

3 151 β HGF basic Fibroblast Growth Factor bfgf

4 152 HOX IL- IL- R c-jun JunB KGF GM-CSF DKK Dickkopf Wnt Wnt-β DKK PAR Protease activated receptor DKK DKK PAR

5 153 β β ml ml

6 154 National Cancer Institute, National Institutes of Health USA Vincent J. Hearing Yamaguchi Y, Yoshikawa K. Cutaneous wound healing: an update. J Dermatol. ; : -. Yamaguchi Y, Hosokawa K, Nakatani Y, et al. Gastrin-releasing peptide, a bombesin-like neuropeptide, promotes cutaneous wound healing. Dermatol Surg. ; : -. Yoshida S, Yamaguchi Y, Itami S, et al. Neutralization of hepatocyte growth factor leads to retarded cutaneous wound healing associated with decreased neovascularization and granulation tissue formation. J Invest Dermatol. ; : -. Takahashi Y, Yamaguchi Y, Itoh K, et al. Intractable wounds caused by pyoderma gangrenosum in a patient with critical limb ischemia treated with cyclosporine and adjuvant sympathectomy. Dermatol Surg. ; : -. Hanafusa T, Yamaguchi Y, Tani M, et al. Intractable wounds caused by calcific uremic arteriolopathy treated with bisphosphonates. J Am Acad Dermatol. ; : -. Nishimura Y, Yamaguchi Y, Tomita Y, et al. Epithelioid sarcoma on the foot masquerading as an intractable wound for years. Clin Exp Dermatol.. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. ; : -. Yamaguchi Y, Kubo T, Murakami T, et al. Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing. Br J Dermatol. ; : -. Yamaguchi Y, Yoshida S, Sumikawa Y, et al. Rapid healing of intractable diabetic foot ulcers with exposed bones following a novel therapy of exposing bone marrow cells and then grafting epidermal sheets. Br J Dermatol. ; : -. Yamaguchi Y, Sumikawa Y, Yoshida S, et al. Prevention of amputation caused by rheumatic diseases following a novel therapy of exposing bone marrow, occlusive dressing and subsequent epidermal grafting. Br J Dermatol. ; : -. Yamaguchi Y, Hearing VJ, Itami S, et al. Mesenchymal-epithelial interactions in the skin: aiming for site-specific tissue regeneration. J Dermatol Sci. ; : -. Yamaguchi Y, Crane S, Zhou L, et al. Lack of coordinate expression of the alpha I and alpha III procollagen genes in fibroblast clonal cultures. Br J Dermatol. ; : -. Chang HY, Chi JT, Dudoit S, et al. Diversity, topo-

7 155 graphic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A. ; : -. Ando Y, Yamaguchi Y, Hamada K, et al. Expression of mrna for androgen receptor, alphareductase and beta-hydroxysteroid dehydrogenase in human dermal papilla cells. Br J Dermatol. ; : -. Yamaguchi Y, Takahashi K, Zmudzka BZ, et al. Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. Faseb J. ; : -. Yamaguchi Y, Brenner M, Hearing VJ. The regulation of skin pigmentation. J Biol Chem. ; : -. Suzuki K, Yamaguchi Y, Villacorte M, et al. Embryonic hair follicle fate change by augmented beta-catenin through Shh and Bmp signaling. Development. ; : -. Yamaguchi Y, Hearing VJ. Physiological factors that regulate skin pigmentation. Biofactors. ; : -. Yamaguchi Y, Hearing VJ. Chapter : Melanocyte distribution and function in human skin: effects of UV radiation. In: Hearing VJ, Leong SPL, eds. From melanocytes to malignant melanoma: the progression to malignancy. Totowa: Humana Press; : -. Yamaguchi Y, Itami S, Tarutani M, et al. Regulation of keratin in nonpalmoplantar keratinocytes by palmoplantar fibroblasts through epithelialmesenchymal interactions. J Invest Dermatol. ; : -. Yamaguchi Y, Itami S, Watabe H, et al. Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol. ; : -. Yamaguchi Y, Passeron T, Watabe H, et al. The effects of dickkopf on gene expression and Wnt signaling by melanocytes: mechanisms underlying its suppression of melanocyte function and proliferation. J Invest Dermatol. ; : -. Yamaguchi Y, Passeron T, Hoashi T, et al. Dickkopf DKK regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. Faseb J. ; : -. Yasuda M, Miyachi Y, Ishikawa O, Takahashi K. Spatial expressions of fibronectin and integrins by human and rodent dermal fibroblasts. Br J Dermatol. ; : -. Yamaguchi Y, Hosokawa K, Sumikawa Y, et al. The use of autologous and bioengineerred epidermis to control fibrosis and impove cosmesis. Wounds. ; : -. Yamaguchi Y, Kubo T, Tarutani M, et al. Epithelial-mesenchymal interactions in wounds: treatment of palmoplantar wounds by nonpalmoplantar pure epidermal sheet grafts. Arch Dermatol. ; : -. Yamaguchi Y, Hosokawa K, Kawai K, et al. Involvement of keratinocyte activation phase in cutaneous graft healing: comparison of full-thickness and split-thickness skin grafts. Dermatol Surg. ; : -. Yamaguchi Y, Itami S, Yoshikawa K. Chapter : Skin grafting: surgical technique. In: Falabella A, Kirsner R, eds. Wound healing: science and practice. New York: Marcel Dekker; : -. Hanafusa T, Yamaguchi Y, Nakamura M, et al. Establishment of suction blister roof grafting by injection of local anesthesia beneath the epidermis: less painful and more rapid formation of blisters. J Dermatol Sci. ; : -.

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STUDY. Epithelial-Mesenchymal Interactions in Wounds. Treatment of Palmoplantar Wounds by Nonpalmoplantar Pure Epidermal Sheet Grafts

STUDY. Epithelial-Mesenchymal Interactions in Wounds. Treatment of Palmoplantar Wounds by Nonpalmoplantar Pure Epidermal Sheet Grafts STUDY Epithelial-Mesenchymal Interactions in Wounds Treatment of Palmoplantar Wounds by Nonpalmoplantar Pure Epidermal Sheet Grafts Yuji Yamaguchi, MD, PhD; Tateki Kubo, MD; Masahito Tarutani, MD, PhD;