Publications (9)11.47 Total impact
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Article: Improvement of hind-limb paralysis following traumatic spinal cord injury in rats by grafting normal human keratinocytes: new cell-therapy strategy for nerve regeneration.
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ABSTRACT: Somatic (adult) stem cells are thought to have pluripotency, just as do embryotic stem (ES) cells. We investigated the possibility that grafted epithelial keratinocytes could induce spinal cord regeneration in an animal model of spinal cord injury (SCI). Normal human keratinocytes were cultured by the routine technique, and normal human dermal fibroblasts were cultured by a similar method as a control group. SCI model was prepared by dropping a 10-g weight onto the exposed spinal cord of rats from a height of 25 mm, and 8 days later, the cultured cells were grafted into the injury site. Motor function was significantly improved in the cultured-keratinocyte-grafted group compared with that in the fibroblast-grafted group. After functional observation, human nestin- and nuclei-positive cells were found at the grafted spinal cord. Grafted cultured keratinocytes induced in vitro morphological changes in the neural induction medium. These results indicated one possibility that some of the grafted cultured keratinocytes survived and could have contributed to neural regeneration. On the other hand, it should be noted that the grafted cultured keratinocytes secreted a large amount of enzymes and/or growth factors. Therefore, another possibility is that the grafted-keratinocyte-derived factors could induce survived cell growth and endogenous neural differentiation of spinal-nerve-derived stem cells surrounding the injured spinal cord, leading to functional recovery. Epithelial stem cell therapy may be applied clinically in the near future to treat SCI.Journal of Artificial Organs 08/2011; 14(4):375-80. · 1.59 Impact Factor -
Article: Activation of heparanase by ultraviolet B irradiation leads to functional loss of basement membrane at the dermal-epidermal junction in human skin.
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ABSTRACT: Recently, we reported that heparanase plays important roles in barrier-disrupted skin, leading to increased interaction of growth factors between epidermis and dermis and facilitating various cutaneous changes, including epidermal hyperplasia and wrinkle formation. However, the role of heparanase in sun-exposed skin remains unknown. Here, we show that heparanase in human keratinocytes is activated by ultraviolet B (UVB) exposure and that heparan sulfate of perlecan is markedly degraded in UVB-irradiated human skin. The degradation of heparan sulfate resulted in a marked reduction of binding activity of the basement membrane for vascular endothelial growth factor, fibroblast growth factor-2 and -7 at the dermal-epidermal junction. Degradation of heparan sulfate was observed not only in acutely UVB-irradiated skin, but also in skin chronically exposed to sun. Interestingly, heparan sulfate was found to be degraded in sun-exposed skin, but not in sun-protected skin. These findings suggest that chronic UVB exposure activates heparanase, leading to degradation of heparan sulfate in the basement membrane and increased growth factor interaction between epidermis and dermis. These changes may facilitate photo-aging.Archives for Dermatological Research 01/2011; 303(4):253-61. · 2.28 Impact Factor -
Article: Application for regenerative medicine of epithelial cell culture-vistas of cultured epithelium.
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ABSTRACT: This review describes culture techniques for the epithelial system as well as trends in the clinical application of cultured keratinocytes in our department and the possibility of applying the techniques to other organs. Cultured epithelium and cultured dermis in particular have considerably preceded regeneration of other organs in the field of regenerative medicine. Since 1988 we have grafted cultured keratinocytes by the Rheinwald-Green modified method in at least 500 patients with large skin defects. As a result of the establishment of a culture technique for individual patients, it is now possible to prepare enough regenerated epithelium to cover the body surface area of as many as 10 adult patients in approximately three weeks after collecting 1 cm(2) of skin, and then remaining cultured keratinocytes can be cryo-preserved for two-stage dermatoplasty at another site. This procedure makes it possible to avoid frequent skin collection from the same patient and thereby improves patients' quality of life and activities of daily living. On the other hand, to solve the problem of regenerated epithelium shrinking and problems with graft efficiency on dermis defect lesion, we have developed a proteinase-resistant regenerated dermis by mixing a certain protein with a fibrin scaffold. Recently we also took the initiative in grafting hybrid-type regenerated trachea in an animal experiment by using the epithelial and dermal cell culture technique, and some results of the graft were obtained.Congenital Anomalies 10/2006; 46(3):129-34. -
Article: [Treatment of burns by grafting of cultured epithelium].
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ABSTRACT: The most serious problem in the treatment of extensive burns is a lack of sufficient healthy skin for coverage of the affected area. Several methods have been used for the coverage of extensive burn wounds. The grafting of cultured epithelium is a potentially effective method for a permanent covering of the wound, particularly in patients with extensive burns. The condition of the recipient site is the most important factor in the success of cultured epithelium grafting and the preservation of the dermis or dermal components in the burned area will enhance the grafting process. We recommend that prior to the grafting of cultured epithelial cells, the burn wounds should be excised and covered with an allograft or artificial dermis during the first 2 weeks after admission. An allograft of cultured epithelium is also useful. This method accelerates the epithelialization of both the burn and donor sites. It is expected that cultured epithelial cell grafts will prove to be an effective treatment not only for extensive burns but also to epithelialize small area burn wounds and resurfaced burn scars.Nippon Geka Gakkai zasshi 01/2006; 106(12):750-4. -
Article: Re-epithelialisation and the possible involvement of the transcription factor, basonuclin.
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ABSTRACT: This article briefly summarises the basic mechanism of re-epithelialisation and discusses the possible role of the cell-type-specific transcription factor, basonuclin. Re-epithelialisation is initiated by a signal resulting from the absence of neighbouring cells at the wound edge. Basal cells at the wound edge become flattened and lose their intercellular desmosomes and substratum attachment. The amount of cytoplasmic actinomyosin filaments that insert into the new adhesion complexes is increased, and contraction of those filaments produces cell movement. The epithelial cells at the wound edge migrate on a provisional matrix using the newly expressed integrin receptors. Once re-epithelialisation is complete, the epithelial cells revert to the normal phenotype of basal epidermal cells, firmly attach to the newly developed basement membrane zone through hemidesmosomes and resume standard differentiation. Protein synthesis increases in the epidermal cells at the wound edge during re-epithelialisation. Active protein synthesis requires accelerated transcription of ribosomal RNA genes. The transcription factor basonuclin binds to the ribosomal RNA gene promoter and increases the transcription of the genes. Therefore, it is speculated that basonuclin in epithelial cells is required in the process of re-epithelialisation.International Wound Journal 07/2004; 1(2):135-40. · 1.46 Impact Factor -
Article: Permanent restoration of human skin treated with cultured epithelium grafting--wound healing by stem cell based tissue engineering--.
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ABSTRACT: The technique of epidermal cell culture developed by Green and colleagues made a breakthrough in the treatment of massive wounds in vivo with grown cells in vitro. In the past two decades, progress of culture methods and clinical practice have been made and now it is possible to treat extensive skin defect with large amounts of cultured epithelium. Since 1985, we have been successfully used cultured epidermis as autografts for the permanent coverage of full-thickness burn wounds or excised burn scars, giant nevi, tattoos and so on. Furthermore, cultured epidermis has been available as allografts to promote the healing of chronic skin ulcers or deep dermal burn. In this paper we describe our clinical experience of cultured epithelium grafting for the treatment of wounds and predict new trial of wound management and regeneration based on tissue engineering concept.Human Cell 10/2002; 15(3):118-28. · 1.27 Impact Factor -
Article: Gigantomastia induced by bucillamine.
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ABSTRACT: Drug-induced mammary hyperplasias have been reported as rare complications of D-penicillamine and Neothetazone. The authors report the first case of bucillamine-induced giant mammary hyperplasia. Bucillamine is used as an antirheumatic drug that is structurally analogous to D-penicillamine. A 25-year-old woman with rheumatoid arthritis for the past 5 years started to develop gradual enlargement of her breasts 15 months before presentation. She had been on a combined treatment of steroid and lobenzarit disodium for the first 3 years, and then continued with a combined treatment of steroid and bucillamine for the following years until she was found to have pulmonary tuberculosis, at which time the steroid was suspended 10 months before she visited the authors' clinic. An almost total breast reduction was performed; 5 kg of right breast tissue and 7 kg of left breast tissue were excised. Retrospectively, bucillamine was believed to be the cause of the giant hypertrophy because of its structural similarity to D-penicillamine, which was the subject of an abundance of reports of mammary hyperplasia.Annals of Plastic Surgery 09/2002; 49(2):193-5. · 1.32 Impact Factor -
Article: Determination of nitrotyrosine and related compounds in biological specimens by competitive enzyme immunoassay.
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ABSTRACT: A gas mediator, nitric oxide is converted to peroxynitrite in the presence of superoxide anion. Peroxynitrite is a potent oxidant, which injures various tissues and organs by nitration of the tyrosine residues of proteins, and it enhances the late response of inflammation. The determination of nitrated tyrosine, nitrotyrosine, which is a stable final metabolite of peroxynitrite, provides an important indicator of tissue disorders caused by peroxynitrite. This paper reports a competitive solid-phase immunoassay for measuring nitrotyrosine in various biological specimens. In this study, peroxidase-conjugated nitrotyrosine was prepared by reaction of nitrotyrosine with 1,4-benzoquinone treatment, and then it was allowed to compete with nitrotyrosine on an anti-nitrotyrosine antibody-coated 96-well multiplate. No amino acids or related compounds tested in the experiments interfered with the immune reaction of nitrotyrosine, except cysteine, which only slightly inhibited the immune reaction at the concentrations higher than 1000 times the concentration of nitrotyrosine. The limit of detection of free nitrotyrosine was approximately 500 pg/mL (2 nM) at a competition ratio (B/B(o)%) of 80%. The newly developed enzyme immunoassay (EIA) method was used for assay of nitrotyrosine in biological specimens, with the following results: (i) Lipopolysaccharide (LPS) activation of RAW264.7 cells induced a significant increase in nitrotyrosine production compared to that with nonactivated cells. N(omega)-nitro-L-arginine methyl ester decreased nitrotyrosine production with either LPS-activated or nonactivated RAW cells. There is a relationship between nitrotyrosine production and nitrite ion. (ii) The nitrotyrosine level detected in the plasma specimens from healthy volunteers was 35.21 +/- 4.87 ng/mL (135.4 +/- 18.7 nM). (iii) The concentration of nitrotyrosine in the nasal lavage fluid of allergic rhinitis patients was 41.40 +/- 20.96 ng/mL (159.02 +/- 80.6 nM). Thus, the EIA method combines sensitivity and specificity with the ability to process a large number of specimens to quantify nitrotyrosine produced with in vivo and in vitro sources.Nitric Oxide 09/2002; 7(1):11-7. · 3.55 Impact Factor -
Article: Clinical application of autologous cultured epithelia for the treatment of burns and disfigurement of skin surfaces.
Methods in molecular biology (Clifton, N.J.) 02/2002; 188:185-96.
Top co-authors
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Institutions
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2002–2011
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St. Marianna University School of Medicine
- Department of Plastic and Reconstructive Surgery
Kawasaki, Kanagawa-ken, Japan -
Tokyo Women's Medical University
Tokyo, Tokyo-to, Japan
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