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Clinical trial of allogeneic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa*

2004; Elsevier BV; Volume: 50; Issue: 5 Linguagem: Inglês

10.1016/j.jaad.2003.08.013

1097-6787

Toshio Hasegawa, Yasushi Suga, Masayuki Mizoguchi, Shigaku Ikeda, Hideoki Ogawa, Kentaro Kubo, Hiromichi Matsui, Shizuko Kagawa, Yoshimitsu Kuroyanagi,

Wound Healing and Treatments

Previously, various kinds of biological dressing, including autologous and allogeneic grafts, have been used to treat intractable ulcers in patients with recessive dystrophic epidermolysis bullosa (RDEB),1Carter D.M Lin A.N Varghese M.C Caldwell D Pratt L.A Eisinger M Treatment of junctional epidermolysis bullosa with epidermal autografts.J Am Acad Dermatol. 1987; 17: 246-250Abstract Full Text PDF PubMed Scopus (107) Google Scholar, 2McGraph J.A Schofield O.M.V Ishida-Yamamoto A O'Grady A Mayou B.J Navsaria H et al.Cultured keratinocyte allografts and wound healing in severe dystrophic epidermolysis bullosa.J Am Acad Dermatol. 1993; 29: 407-419Abstract Full Text PDF PubMed Scopus (38) Google Scholar with variable results. In the present study, we employ an allogeneic cultured dermal substitute (CDS) prepared by plating normal human fibroblasts on a double-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col)3Kuroyanagi Y Yamada N Yamashita R Uchinuma E Tissue-engineered product allogeneic cultured dermal substitute composed of spongy collagen with fibroblasts.Artif Organs. 2001; 25: 180-186Crossref PubMed Scopus (63) Google Scholar, 4Kubo K Kuroyanagi Y Spongy matrix of hyaluronic acid and collagen as a cultured dermal substitute evaluation in animal test.J Artif Organs. 2003; 6: 64-70Crossref PubMed Scopus (43) Google Scholar to treat RDEB (Hallopeau-Siemens type) patients with intractable skin ulcers. Three patients diagnosed with RDEB on the basis of clinical and histological findings had persistent ulcers on the lower leg or forearm, accompanied by debilitating pain. The condition resisted conservative treatment for more than 10 months. The wound bed of the ulcers was filled with dry, pale, and fibrous tissue (Fig 1, a and d). When the CDS application was repeated twice a week for 2 to 6 weeks, abundant granulation was noticed on the wound surface within a week (Fig 1, b and e). Epithelialization began from the margins of the ulcer after four weeks (Fig 1, c and f). Cryopreserved human fibroblasts in the CDS is able to release the vascular endothelial growth factor and fibronectin, which in turn induce prompt granulation in the wound bed.3Kuroyanagi Y Yamada N Yamashita R Uchinuma E Tissue-engineered product allogeneic cultured dermal substitute composed of spongy collagen with fibroblasts.Artif Organs. 2001; 25: 180-186Crossref PubMed Scopus (63) Google Scholar, 4Kubo K Kuroyanagi Y Spongy matrix of hyaluronic acid and collagen as a cultured dermal substitute evaluation in animal test.J Artif Organs. 2003; 6: 64-70Crossref PubMed Scopus (43) Google Scholar, 5Kubo K, Kuroyanagi Y. Characterization of cultured dermal substitute composed of spongy matrix of hyaluronic acid and collagen combined with fibroblasts. J Artif Organs 2003;6:138-44Google Scholar 'In addition, the HA molecule in the matrix is described as having a high capacity for hydrating wound beds, and the Col molecule as acting as a chemoattractant for fibroblasts.3Kuroyanagi Y Yamada N Yamashita R Uchinuma E Tissue-engineered product allogeneic cultured dermal substitute composed of spongy collagen with fibroblasts.Artif Organs. 2001; 25: 180-186Crossref PubMed Scopus (63) Google Scholar, 4Kubo K Kuroyanagi Y Spongy matrix of hyaluronic acid and collagen as a cultured dermal substitute evaluation in animal test.J Artif Organs. 2003; 6: 64-70Crossref PubMed Scopus (43) Google Scholar This study indicates that the use of allogeneic CDS is a promising novel treatment option for severe skin defects in individuals with RDEB.