title: Treatment of refractory cutaneous ulcers with mixed sheets consisting of peripheral blood mononuclear cells and fibroblasts.
abstract: The purpose of this study was to confirm the therapeutic effects of mixed sheets consisting of peripheral blood mononuclear cells (PBMNCs) and fibroblasts on cutaneous skin ulcers. Vascular endothelial growth factor (VEGF) secretion in mixed cell sheets was much higher than in PBMNCs and fibroblasts. Concerning the mechanism, transforming growth factor beta 1 and platelet-derived growth factor BB secreted from PBMNCs enhanced VEGF production in fibroblasts. In wounds created on the backs of diabetic mice, the therapeutic effect of mixed cell sheets was similar to that of daily treatment with trafermin, a recombinant human basic fibroblast growth factor. Although abnormal granulation tissue and inflammatory cell infiltration were observed in trafermin-treated wounds, the transplantation of mixed cell sheets resulted in the natural anatomy of subcutaneous tissues. The expression patterns of identical wound-healing factors in wounds were different between mixed sheet-transfected and trafermin-treated animals. Because mixed cell sheets transplanted into full-thickness skin defects were eliminated in hosts by day 21 in syngeneic transplantation models, allogeneic transplantation was performed using mice with different genetic backgrounds. The wound-healing rates were similar between the mixed cell sheet and trafermin groups. Our data indicated that mixed cell sheets represent a promising therapeutic material for cutaneous ulcers.
authors.affiliation: Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Takeuchi
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Samura
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Tamami
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Nishimoto
authors.affiliation: Institute of Laboratory Animals, Yamaguchi University, Ube, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murata
authors.affiliation: Center for Regenerative Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.|Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Hosoyama
authors.affiliation: Department of Surgery and Clinical Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000818:Animals; D000077214:Becaplermin; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D005346:Fibroblast Growth Factors / Q000627:therapeutic use; D005347:Fibroblasts / Q000637:transplantation*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis; D016038:Skin Transplantation; D012883:Skin Ulcer / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017768:Skin, Artificial; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing; D014998:Y Chromosome / Q000235:genetics
chemical_list: D010446:Peptide Fragments; D020574:Proto-Oncogene Proteins c-sis; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000077214:Becaplermin; C114444:trafermin; D005346:Fibroblast Growth Factors