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Dive into the research topics where Kozo Akino is active.

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Featured researches published by Kozo Akino.


British Journal of Dermatology | 2005

Human mesenchymal stem cells successfully improve skin-substitute wound healing.

Hiroshi Nakagawa; Sadanori Akita; Masashi Fukui; Tohru Fujii; Kozo Akino

Background  Large or deteriorated skin defects are sometimes life threatening. There is increasing evidence that adult stem cells are useful for tissue regeneration. Human mesenchymal stem cells (hMSCs) are self‐renewing and are potent in differentiating into multiple cells and tissues.


Wound Repair and Regeneration | 2004

Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor

Sadanori Akita; Masashi Fukui; Hiroshi Nakagawa; Tohru Fujii; Kozo Akino

To facilitate bone healing in difficult circumstances, and to replace conventional therapeutic modalities, highly purified bone marrow‐derived human mesenchymal stem cells (hMSCs) were investigated for induction of their osteogenic lineage upon provision of cytokine cues in vitro and in the cranial defect model in vivo. Alkaline phosphatase‐expressing cells were most frequently observed when the hMSCs were treated with 2.5 ng/ml of basic fibroblast growth factor (bFGF) and 50 ng/ml of bone morphogenetic protein (BMP)‐2 for 4 days in culture after a 6‐day incubation in osteogenic medium containing dexamethasone, ascorbic acid‐2‐phosphate, and β‐glycerophosphate. Four‐millimeter full‐thickness cranial defect wounds were made in male nude rats (F344/NJCl‐rnu), whose deficit in the T cell compartment prevented T‐cell–mediated cellular rejection. The animals were treated for 4 weeks with hMSCs and application of 10 µg each of bFGF and BMP‐2 that had been soaked into a gelatin sponge carrier. Significant bone mineral density was observed by dual X‐ray absorptiometry and this treatment also produced histologically mature osteocytes surrounded by both osteoblasts and osteoclasts expressing alkaline phosphatase and osteocalcin. The bone mineral densities and histological structures were matched at 8 weeks post‐transplantation. Therefore, human bone marrow‐derived mesenchymal stem cells are able to differentiate into an osteogenic lineage upon cytokine stimulation and accelerate healing in a nude rat cranial bone healing model.


Wound Repair and Regeneration | 2008

Basic fibroblast growth factor accelerates and improves second-degree burn wound healing.

Sadanori Akita; Kozo Akino; Toshifumi Imaizumi; Akiyoshi Hirano

Second‐degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second‐degree burn patients (average 57.8 ± 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 ± 0.9 days from the burn injury, compared with non‐bFGF use (12.0 ± 2.2 vs. 15.0 ± 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF‐treated and non‐bFGF–treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF‐treated scars than non‐bFGF–treated scars (0.23 ± 0.10 vs. 0.14 ± 0.06 mm, 0.59 ± 0.20 vs. 0.49 ± 0.15 mm: scar extension, scar elasticity, bFGF vs. non‐bFGF, p<0.01). The durometer reading was significantly lower in bFGF‐treated scars than in non‐bFGF–treated scars (16.2 ± 3.8 vs. 29.3 ± 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF‐treated than in non‐bFGF–treated scars (p<0.01).


American Journal of Pathology | 1999

Overexpression of Insulin-Like Growth Factor-1 (IGF-I) Receptor and the Invasiveness of Cultured Keloid Fibroblasts

Hiroshi Yoshimoto; Hiroshi Ishihara; Akira Ohtsuru; Kozo Akino; Ryuichi Murakami; Hiroaki Kuroda; Masahiro Ito; Tohru Fujii; Shunichi Yamashita

Keloid is a dermal fibroproliferative tissue of unknown etiology. Protein tyrosine kinases (PTKs) play an important role in the regulation of cell growth and differentiation. Activation of PTK cascades in keloid fibroblasts is thought to be closely linked to abnormal cell proliferation and migration. We determined the expression profile of PTK genes in normal skin and keloid fibroblasts using the homology cloning method with a degenerated primer. Eight PTK genes were expressed among a total of 46 receptor-type clones. The most abundant type of PTK receptors was the platelet-derived growth factor receptor in both fibroblasts. However, insulin-like growth factor-I receptor (IGF-IR) was overexpressed only in keloid-derived fibroblasts (9 of 24). Immunohistochemical analysis confirmed the high expression of IGF-IR in keloid fibroblasts, but not in normal fibroblasts. To examine the functional properties of the IGF-I/IGF-IR pathway, we investigated cell proliferation and invasion activities of both types of fibroblasts. The mitogenic effect of IGF-I on both fibroblasts was very weak compared with serum stimulation. In contrast, the invasive activity of keloid fibroblasts was markedly increased in the presence of IGF-I, and inhibited by a neutralizing antibody against IGF-IR. Our results indicate the involvement of activated IGF-I/IGF-IR in the pathogenesis of keloid by enhancing the invasive activity of fibroblasts.


Health Physics | 2010

Mesenchymal stem cell therapy for cutaneous radiation syndrome.

Sadanori Akita; Kozo Akino; Akiyoshi Hirano; Akira Ohtsuru; Shunichi Yamashita

Systemic and local radiation injuries caused by nuclear power reactor accidents, therapeutic irradiation, or nuclear terrorism should be prevented or properly treated in order to improve wound management and save lives. Currently, regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with a local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells and adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and were tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who were suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. In the experiments, the hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. In vivo, 4 Gy rat whole body irradiation demonstrated that sustained marrow stromal (mesenchymal stem) cells survived in the bone marrow. Immediate artificial dermis application impregnated with cells and the cytokine over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angiogenesis, architected dermal reconstitution, and less inflammatory epidermal recovery. Detailed understanding of underlying diseases and rational reconstructive procedures brings about good outcomes for difficult irradiated wound healing. Adipose-derived stem cells are also implicated in the limited local injuries for short cell harvesting and processing time in the same subject.


Journal of Burn Care & Research | 2006

The quality of pediatric burn scars is improved by early administration of basic fibroblast growth factor.

Sadanori Akita; Kozo Akino; Toshifumi Imaizumi; Katsumi Tanaka; Kuniaki Anraku; Hiroki Yano; Akiyoshi Hirano

Pediatric burn wounds can be problematic because an accurate evaluation is difficult as the result of anatomically immature vasculature or immobilization failure, especially in patients with second-degree burns, and because the burn surface areas and the burn depth tend to worsen over the course of time. Delayed wound healing results in unsightly scarring, such as hypertrophic scars, which are problematic both esthetically and functionally. Among cytokines and growth factors, basic fibroblast growth factor (bFGF) is clinically proven, having demonstrated accelerated acute and chronic wound healing. Accelerated wound healing may lead to improved scarring. To elucidate the effects of bFGF on second-degree pediatric burn wounds, a comparative study was performed. A total of 20 pediatric patients ranging from 8 month to 3 years (average 1 year, 3 months ± 6 months) who suffered from the burns by various causes were divided into two groups, conventional (n = 10) and treatment with bFGF (n = 10). A moisture meter, used to objectively measure the stratum corneum and epithelial—mesenchymal functions, was used to assess scars at least 1 year after wound healing. Clinical evaluation of pigmentation, pliability, height, and vascularity demonstrated significant differences between conventional and bFGF-treated scars (1.7 ± 0.55 vs 0.7 ± 0.58, 2.4 ± 0.82 vs 1.1 ± 0.69, 1.8 ± 0.66 vs 0.5 ± 0.57, 1.9 ± 0.63 vs 0.8 ± 0.68; conventional vs bFGF-treated, pigmentation, pliability, height, and vascularity, respectively, P < .01). The effective contact coefficient was significantly greater in conventional wounds than bFGF-treated wounds (14.6 ± 1.68 % vs 8.7 ± 2.82 %; conventional vs bFGF, P < .01) and bFGF-treated wounds demonstrated significantly less transepidermal water loss values than conventional treatment (8.3 ± 1.90 g/m2/h vs 5.7 ± 1.85 g/m2/hr; conventional vs bFGF, P < .01). Pediatric burn patients treated with bFGF showed less damaging function of the stratum corneum after healing both in clinical assessment and moisture meter analysis.


Stem Cells International | 2010

Noncultured autologous adipose-derived stem cells therapy for chronic radiation injury.

Sadanori Akita; Kozo Akino; Akiyoshi Hirano; Akira Ohtsuru; Shunichi Yamashita

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.


Wound Repair and Regeneration | 2003

Bone morphogenetic protein-2 regulates proliferation of human mesenchymal stem cells

Kozo Akino; Takao Mineta; Masashi Fukui; Tohru Fujii; Sadanori Akita

Human mesenchymal stem cells obtained from the iliac crest of a single donor were investigated for cell proliferation, cell cycle profile, gene expression, and ultrastructural changes using electron microscopy. The human mesenchymal stem cells significantly increased their cell number by day 2 after treatment with bone morphogenetic protein‐2 alone, or basic fibroblast growth factor alone or combinations of both proteins under serum‐free conditions (p < 0.01). The human mesenchymal stem cells showed marked expression of cell nuclear antigen, notably at day 1, and pituitary tumor transforming gene throughout the experiment, suggesting cell cycle progression by bone morphogenetic protein‐2 treatment. In addition, strong cellular nuclear bromodeoxyuridine incorporation was seen by immunocytochemistry. Fluorescence‐activated cell sorting also showed a similar pattern of cell cycle progression with bone morphogenetic protein‐2 treatment in serum‐free medium and 10% fetal bovine serum treatment. The bone morphogenetic protein‐2–treated human mesenchymal stem cells showed heterochromatin in the nucleus, suggesting cell differentiation, and well‐developed granular endoplasmic reticulum, indicative of protein production. Overall, the human mesenchymal stem cells successfully proliferated with appropriate cell cycle progression and the cell ultrastructural morphology suggested marked nuclear and granular endoplasmic reticulum induction by bone morphogenetic protein‐2 treatment in serum‐free medium. (WOUND REP REG 2003;11:354–360)


Journal of Trauma-injury Infection and Critical Care | 2008

A Basic Fibroblast Growth Factor Improves Lower Extremity Wound Healing With a Porcine-Derived Skin Substitute

Sadanori Akita; Kozo Akino; Katsumi Tanaka; Kuniaki Anraku; Akiyoshi Hirano

BACKGROUND Although a number of cytokine or growth factor therapies for wound acceleration have been reported, few mentioned the quality of the outcome. The lower extremity is important in esthetics as well as in function, because it is exposed. Recently, a growth factor, namely basic growth factor (bFGF) is widely used for difficult wound healing with a porcine-derived bilayered artificial dermis for better wound closure. Thus, their combination use was tested clinically. METHODS Sequential lower extremity reconstruction by an artificial dermis with or without bFGF administration and secondary split-thickness skin grafting was measured for hardness using a durometer, and the moisture parameters assessed such as effective contact coefficient, transepidermal water loss (TEWL), water content and thickness using a moisture meter for at least 6 months after the final procedure and compared with normal skin control. RESULTS There was significantly less skin hardness using a durometer in bFGF treatment compared with non-bFGF treatment (16.2 +/- 3.83 vs. 29.2 +/- 4.94, p < 0.01). Effective contact coefficient, TEWL, water content, and thickness in non-bFGF treatment were all significantly greater than those in bFGF treatment, whereas water content and thickness in bFGF treatment were comparable with those of the control. CONCLUSION The use of bFGF as artificial dermis for extensive and deeper tissue loss coverage demonstrated better reconstruction quality in terms of hardness using a durometer and the function of the stratum corneum by moisture analysis.


Journal of Craniofacial Surgery | 2007

Combined surgical excision and radiation therapy for keloid treatment.

Sadanori Akita; Kozo Akino; Aya Yakabe; Toshifumi Imaizumi; Katsumi Tanaka; Kuniaki Anraku; Hiroki Yano; Akiyoshi Hirano

Various methods have been attempted for the treatment and management of keloids; however, there is little satisfactory clinical evidence in long-term follow ups. Also, there is a preference for occurrence and recurrence in anatomic location. Usually anatomic locations with higher regional tension and more sebaceous glands are inclined toward pathogenesis. Thirty-eight keloids treated with combined surgical excision and postoperative irradiation, using electron beams with only a 10-mm opening by lead shielding, were investigated at a mean follow up of 4.4 ± 2.5 years (range, 1-9 years) at a single institute. Ten locations such as the ear (n = 6), neck (n = 3), and upper lip (n = 1) were among the craniofacial locations. The hardness of the keloids and posttreatment scars was clinically and objectively tested with the Vancouver scar scale and a durometer, which is often used for the industrial measurement of thread balls and rubber. At a mean of 4.4 ± 2.5 years of follow up, the clinical characteristics of the scars were significantly better posttreatment as 2.6 ± 0.5 versus 1.0 ± 0.6, 3.7 ± 0.7 versus 1.7 ± 0.7, 2.9 ± 0.4 versus 1.3 ± 0.5, and 2.7 ± 0.5 versus 1.3 ± 0.5 (keloid scars versus posttreatment scars: pigmentation, pliability, height and vascularity, respectively, P < 0.01). The durometer readings were significantly lower posttreatment, 15.2 ± 3.9 versus 7.7 ± 2.9 (keloid scars versus posttreatment scars, P < 0.01). The recurrence rate was 21.2% overall with none in craniofacial locations. Therefore, the combined treatment of surgical excision and postoperative electron beam irradiation is effective for scar quality and reducing the recurrence rate in long-term follow up.

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Akira Ohtsuru

Fukushima Medical University

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