Updated on 2025/03/25

写真a

 
HIGUCHI Shinichi
 
Organization
Nagoya University Hospital Plastic and Reconstructive Surgery Assistant professor of hospital
Title
Assistant professor of hospital
External link

Degree 1

  1. Medical Doctor ( 2005.3 ) 

Research History 3

  1. Nagoya University   Nagoya University Hospital Plastic and Reconstructive Surgery   Assistant professor of hospital

    2020.7

  2. Nagoya City University   Assistant Professor

    2020.4 - 2020.6

  3. University of Pittsburgh   Post doctoral associate

    2017.4 - 2020.3

Education 2

  1. Nagoya University

    2016.4 - 2021.3

  2. Nagoya City University

    1999.4 - 2005.3

Professional Memberships 1

  1. 日本形成外科学会   評議員

    2007.4

Committee Memberships 2

  1. 日本形成外科学会   日本形成外科学会動画審査委員  

    2021.5   

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    Committee type:Academic society

  2. 日本形成外科学会   日本形成外科学会会誌編集委員  

    2021.5   

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    Committee type:Academic society

Awards 2

  1. 国際熱傷学会日本支部会学術賞

    2016   国際熱傷学会  

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    Award type:Award from international society, conference, symposium, etc. 

  2. 国際熱傷学会日本支部会学術賞

    2012   国際熱傷学会  

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    Award type:Award from international society, conference, symposium, etc. 

 

Papers 8

  1. Head and neck free flap reconstruction under the COVID-19 pandemic

    Higuchi, S; Hashikawa, K; Ebisawa, K; Kambe, M; Kamei, Y

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 86 ( 3 ) page: 472 - 478   2024.8

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    Language:English   Publisher:Nagoya Journal of Medical Science  

    High perioperative mortality and complication rates during the coronavirus disease 2019 (COVID-19) pandemic have been reported. In head and neck reconstruction, not only is patient safety important, but the prevention of infection introduced by the surgical team is also important because the procedure is performed in close proximity to the upper respiratory tract. In addition, recent studies have reported an increased risk for thrombus formation after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 vaccination, which is problematic for microsurgical reconstruction procedures. At the authors’ institution, patients undergoing head and neck reconstruction are requested to stay home for 2 weeks and undergo screening tests for COVID-19 before admission. Surgeons use standard personal protective equipment during surgery. There was no significant difference in the rate of total flap necrosis between the COVID-19 and non-pandemic periods or large difference of perioperative complication rates between vaccinated and non-vaccinated patients. No surgery-related infections among the surgical staff were also found.

    DOI: 10.18999/nagjms.86.3.472

    Web of Science

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  2. Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues Open Access

    Oishi, M; Shinjo, K; Takanari, K; Muraoka, A; Suzuki, MM; Kanbe, M; Higuchi, S; Ebisawa, K; Hashikawa, K; Kamei, Y; Kondo, Y

    SCIENTIFIC REPORTS   Vol. 14 ( 1 ) page: 8725   2024.4

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    Language:English   Publisher:Scientific Reports  

    Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

    DOI: 10.1038/s41598-024-59293-z

    Open Access

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  3. A Case of Maffucci Syndrome Reconstructed with Free Fibular Osteocutaneous Flap for Chondrosarcoma in the Upper Arm

    HIGUCHI Shinichi, IKUTA Kunihiro, HASHIKAWA Kazunobu, EBISAWA Katsumi, KAMBE Miki, KAMEI Yuzuru

    Journal of Japanese Society of Reconstructive Microsurgery   Vol. 37 ( 3 ) page: 133 - 136   2024

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    Language:Japanese   Publisher:Japanese Society of Reconstructive Microsurgery  

    <p> A 33-year-old man with Maffucci syndrome developed chondrosarcoma in the left upper arm, which required reconstructive surgery. The left fibula, which had been shortened and underwent bone lengthening in childhood, was not suitable for use as an osteocutaneous flap. Instead, the right fibula, which was free of enchondromas, was considered suitable for use as the donor site for the free-flap reconstruction. One year and three months post-surgery, the transferred bone achieved fusion, and upper limb function was preserved. Maffucci syndrome is characterized by multiple enchondromas and venous malformations due to somatic mosaic mutations in IDH1 and IDH2. Approximately 30% of cases involve malignant transformation of enchondromas. The bone affected by enchondromas is structurally fragile and prone to fractures. In the present study, we used the right fibula, which did not develop enchondromas, as a free flap. The absence of genetic mutations in this bone allowed for normal bone fusion and retention of its strength.</p>

    DOI: 10.11270/jjsrm.37.133

    CiNii Research

  4. Supernatant from activated omentum accelerates wound healing in diabetic mice wound model

    Li, Y; Hashikawa, K; Ebisawa, K; Kambe, M; Higuchi, S; Kamei, Y

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 85 ( 3 ) page: 528 - 541   2023.8

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    Language:English   Publisher:Nagoya Journal of Medical Science  

    Diabetic wounds are considered one of the most frequent and severe complications of diabetes mellitus. Recently, the omentum has been used in diabetic wound healing because of its tissue repair properties. The activated omentum is richer in growth factors than the inactivated, thereby contributing to the wound healing process. To further investigate the effect of activated omentum conditioned medium (aOCM) on diabetic wound healing, we injected supernatant from aOCM, saline-OCM (sOCM), inactivated-OCM (iOCM), and medium (M) subcutaneously upon creation of a cutaneous wound healing model in diabetic mice. Wound area (%) was evaluated on days 0, 3, 5, 7, 9, 11, 14, 21, and 28 post-operation. At 9 and 28 d post-operation, skin tissue was harvested and assessed for gross observation, neovascularization, peripheral nerve fiber regeneration, and collagen deposition. We observed that aOCM enhanced the wound repair process, with significant acceleration of epidermal and collagen deposition in the surgical lesion on day 9. Additionally, aOCM displayed marked efficiency in neovascularization and peripheral nerve regeneration during wound healing. Thus, aOCM administration exerts a positive influence on the diabetic mouse model, which can be employed as a new therapy for diabetic wounds.

    DOI: 10.18999/nagjms.85.3.528

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  5. Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft Open Access

    Furdella, KJ; Higuchi, S; Kim, K; Doetschman, T; Wagner, WR; Vande Geest, JP

    TISSUE ENGINEERING PART A   Vol. 28 ( 13-14 ) page: 640 - 650   2022.7

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    Language:English   Publisher:Tissue Engineering - Part A  

    Transforming growth factor beta 2 (TGFβ2) is a pleiotropic growth factor that plays a vital role in smooth muscle cell (SMC) function. Our prior in vitro work has shown that SMC response can be modulated with TGFβ2 stimulation in a dose dependent manner. In particular, we have shown that increasing concentrations of TGFβ2 shift SMCs from a migratory to a synthetic behavior. In this work, electrospun compliance-matched and hypocompliant TGFβ2-eluting tissue engineered vascular grafts (TEVGs) were implanted into Sprague Dawley rats for 5 days to observe SMC population and collagen production. TEVGs were fabricated using a combined computational and experimental approach that varied the ratio of gelatin:polycaprolactone to be either compliance matched or twice as stiff as rat aorta (hypocompliant). TGFβ2 concentrations of 0, 10, 100 ng/mg were added to both graft types (n = 3 in each group) and imaged in vivo using ultrasound. Histological markers (SMC, macrophage, collagen, and elastin) were evaluated following explanation at 5 days. In vivo ultrasound showed that compliance-matched TEVGs became stiffer as TGFβ2 increased (100 ng/mg TEVGs compared to rat aorta, p < 0.01), while all hypocompliant grafts remained stiffer than control rat aorta. In vivo velocity and diameter were also not significantly different than control vessels. The compliance-matched 10 ng/mg group had an elevated SMC signal (myosin heavy chain) compared to the 0 and 100 ng/mg grafts (p = 0.0009 and 0.0006). Compliance-matched TEVGs containing 100 ng/mg TGFβ2 had an increase in collagen production (p < 0.01), general immune response (p < 0.05), and a decrease in SMC population to the 0 and 10 ng/mg groups. All hypocompliant groups were found to be similar, suggesting a lower rate of TGFβ2 release in these TEVGs. Our results suggest that TGFβ2 can modulate in vivo SMC phenotype over an acute implantation period, which is consistent with our prior in vitro work. To the author's knowledge, this is the first in vivo rat study that evaluates a TGFβ2-eluting TEVG. TGFβ2 affects the SMCs in a vascular graft.

    DOI: 10.1089/ten.tea.2021.0161

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  6. In-vivo assessment of a tissue engineered vascular graft computationally optimized for target vessel compliance Open Access

    Furdella, KJ; Higuchi, S; Behrangzade, A; Kim, K; Wagner, WR; Vande Geest, JP

    ACTA BIOMATERIALIA   Vol. 123   page: 298 - 311   2021.3

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    Language:English   Publisher:Acta Biomaterialia  

    Tissue engineered vascular grafts (TEVGs) have the ability to be tuned to match a target vessel's compliance, diameter, wall thickness, and thereby prevent compliance mismatch. In this work, TEVG compliance was manipulated by computationally tuning its layered composition or by manipulating a crosslinking agent (genipin). In particular, these three acelluluar TEVGs were compared: a compliance matched graft (CMgel - high gelatin content); a hypocompliant PCL graft (HYPOpcl - high polycaprolactone content); and a hypocompliant genipin graft (HYPOgen - equivalent composition as CMgel but hypocompliant via increased genipin crosslinking). All constructs were implanted interpositionally into the abdominal aorta of 21 Sprague Dawley rats (n=7, males=11, females=10) for 28 days, imaged in-vivo using ultrasound, explanted, and assessed for remodeling using immunofluorescence and two photon excitation fluorescence imaging. Compliance matched grafts remained compliance-matched in-vivo compared to the hypocompliant grafts through 4 weeks (p<0.05). Construct degradation and cellular infiltration was increased in the CMgel and HYPOgen TEVGs. Contractile smooth muscle cell markers in the proximal anastomosis of the graft were increased in the CMgel group compared to the HYPOpcl (p=0.007) and HYPOgen grafts (p=0.04). Both hypocompliant grafts also had an increased pro-inflammatory response (increased ratio of CD163 to CD86 in the mid-axial location) compared to the CMgel group. Our results suggest that compliance matching using a computational optimization approach leads to the improved acute (28 day) remodeling of TEVGs. To the authors’ knowledge, this is the first in-vivo rat study investigating TEVGs that have been computationally optimized for target vessel compliance.

    DOI: 10.1016/j.actbio.2020.12.058

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  7. Covalently-Attached, Surface-Eroding Polymer Coatings on Magnesium Alloys for Corrosion Control and Temporally Varying Support of Cell Adhesion

    Chen, YQ; Ye, SH; Zhu, Y; Gu, XZ; Higuchi, S; Wan, GJ; Wagner, WR

    ADVANCED MATERIALS INTERFACES   Vol. 7 ( 15 )   2020.8

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    Publisher:Advanced Materials Interfaces  

    For degradable magnesium (Mg) alloy-based stents it would be desirable to delay early corrosion to maintain mechanical strength. Similarly, early after stent placement reduced thrombogenicity is an important feature, while chronically, endothelial cell adhesion and vessel integration are desirable. In this study, surface eroding polymers of amino-grafted poly(1,3-trimethylene carbonate) (PTMC-NH2) and PTMC-NH2 combined with sulfobetaine bearing polymer PSB (PTMC-NHCO-PSB) are developed, and these polymers are covalently attached onto 6-phosphonohexanoic acid (PHA)-coated AZ31 Mg alloy surfaces in sequence. In vitro degradation testing in ovine plasma shows PTMC, PTMC-NH2, and PTMC-NHCO-PSB cast films experience a gradual thickness and mass loss with maintenance of smooth surfaces, confirming surface erosion behavior. The PTMC-NH2 polymer is firmly bound to the PHA-modified AZ31 surface and demonstrates a resistance to peeling. PTMC, PTMC-NH2, and PTMC-NHCO-PSB coated AZ31 have a lower corrosion rate versus polylactide-co-glycolide coated and untreated AZ31. PTMC-NHCO-PSB coated AZ31 inhibits platelet deposition and smooth muscle cell adhesion and growth, but after 2-week immersion in plasma, this surface supports endothelial cell adhesion and growth. These results suggest PTMC-NHCO-PSB surface eroding coating offers a means of controlling corrosion while providing a temporally varying bio-functionality for biodegradable vascular stent applications.

    DOI: 10.1002/admi.202000356

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  8. Adipose Derived Stem Cells Enhance Cardiac Function Preservation of a Biodegradable Cardiac Patch and Increase Vascularization in Rats With Subacute Myocardial Infarction

    Kashiyama, N; Kormos, RL; Matsumura, Y; Higuchi, S; Silveira, LM; Coyan, G; Bin, JH; D'Amore, A; Wagner, WR

    CIRCULATION   Vol. 138   2018.11

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Presentations 5

  1. 頭頸部再建におけるORBEYEの有用性

    樋口慎一

    日本形成外科学会総会・学術集会  2022.4.22  大阪医科薬科大学形成外科

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    Event date: 2022.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:大阪  

  2. 微小血管吻合における術後合併症を予防するための工夫

    樋口慎一

    日本マイクロサージャリー学会学術集会  2021.12.4  筑波大学形成外科

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    Event date: 2021.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:茨城県つくば市  

  3. 腓骨皮弁におけるドナーの選択の検討

    樋口慎一

    日本頭蓋顎顔面外科学会・学術集会  2021.11.11  東海大学形成外科

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    Event date: 2021.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京  

  4. 感染した補助人工心臓の洗浄中に脳空気塞栓をきたした1例

    樋口慎一

    日本創傷外科学会総会・学術集会  2021.7.16  産業医科大学形成外科

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    Event date: 2021.7

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:福岡  

  5. 複数の皮弁を用いた頭頸部再建の検討

    樋口慎一

    日本形成外科学会総会・学術集会  2021.4.15  獨協医科大学

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    Event date: 2021.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京  

KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. プラズマ活性溶液による難治性潰瘍治療の検討

    Grant number:24K12845  2024.4 - 2027.3

    科学研究費助成事業  基盤研究(C)

    樋口 慎一, 蛯沢 克己, 橋川 和信

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    Authorship:Principal investigator 

    Grant amount:\3250000 ( Direct Cost: \2500000 、 Indirect Cost:\750000 )

    われわれ形成外科の分野の中で創傷治癒と呼ばれる、体が本来持っている傷を修復する仕組みに関する分野は基本的ですが非常に複雑です。大気圧で室温でも適応が可能なプラズマ(低温大気圧プラズマ)が医療分野にも適応されるようになりました。低温大気圧プラズマが治りにくい傷に効くことがわかってきましたが、その機序に関しては未だ不明です。われわれの目的は低温大気圧プラズマが傷が治る過程においてどのような影響を及ぼしているかを検討することです。

  2. 被膜拘縮を抑制するペプチドコーティング乳房インプラントの開発

    Grant number:22K09857  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    神戸 未来, 大石 真由美, 高成 啓介, 亀井 譲, 蟹江 慧, 橋川 和信, 蛯沢 克己, 樋口 慎一

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    Authorship:Coinvestigator(s) 

    乳癌術後の乳房再建術に用いられるシリコンブレストインプラント(以下SBI)には、表面が凹凸のテクスチャード型SBIと、表面滑らかなスムース型SBIがある。テクスチャード型SBIはブレストインプラント関連未分化大細胞性リンパ腫の発症リスクがあり、一方でスムース型SBIは被膜拘縮や破損のリスクがある。本研究ではSBIを機能性ペプチドで加工して、それぞれの問題を予防できるSBIの新規開発を目指している。
    乳房再建用エキスパンダーまたはSBIから周囲被膜組織を採取し、コラゲナーゼを用いて酵素処理後に抽出した細胞群から、蛍光活性化セルソーティング(FACS)でlineageマーカーいずれも陰性かつPDGFRA陽性の細胞群を線維芽細胞として分画し、この細胞群から、筋線維芽細胞へ分化していないCD248low線維芽細胞のみを単離し、培養中に筋線維芽細胞へ分化しないよう、ROCK阻害剤(Y-27632)を添加しながら継代培養して線維芽細胞を作成した。
    この線維芽細胞について、細胞接着ペプチドとして知られている RGD配列をDOPAを用いて修飾し(以下RGD pep)、シリコン材料への接着と線維芽細胞の増殖性を調査した。細胞非接着性wellプレートにRGD pepコーティングによりコラーゲンコーティングと同様の線維芽細胞接着性、増殖性を確認後した。さらに凹凸面シリコンシェル及び平滑面シリコンシェルにRGD pep、コラーゲンでコーティングを行い、コーティングなしのシリコンシェルをコントールとして平滑面及び凹凸面シリコンシェル上での線維芽細胞の接着性と増殖を調査した。3条件共に平滑面より凹凸面の方が線維芽細胞の接着性を認めたが、平滑面RGD pepコーティングが他の条件の平滑面よりも高い細胞接着性を認めた。また他の平滑面シリコンシェルの条件に比べ、高い細胞増殖性を確認された。
    これらの結果を踏まえ、動物実験を行い、テクスチャード型インプラントに見立てた凹凸面シリコンシェル片をPBS、Collagen、Collagen + Tyrosinase、RGDpepで修飾し、ラット背部肉様膜下にそれぞれのを挿入4週後のインプラントの移動と回転を評価し、RGD pep修飾群で最も少ない傾向を得た。
    またこれらのインプラント挿入部に形成された被膜組織について組織学的な解析を行った。
    シリコン表面をコーティングする機能性ペプチドの選択とそれによる、凹凸面・平滑面それぞれのシリコン表面への修飾、またシリコン上での線維芽細胞の接着及び増殖を確認する実験系ができた。最も細胞接着性が強い凹凸面シリコンシェルにRGD pep及び比較郡としてコラーゲンによるコーティングを行い、ラットの背部筋層下に移植してその移動と回転を評価した。4週間時点においてRGD pep修飾群で位置移動や回転が少ない傾向を得た。
    またラットにおいて挿入したシリコン周囲に発生した被膜組織を得られるため組織学的検討を行ったが、今後サンプル数を増やし実験の再現性を確認の上で移植するシリコンの条件や留置期間を変えて調査を進めているが、これと並行して、医療用インプラントへのペプチド修飾方法を検討しているが、現在のコーティング方法であると立体的なインプラントへの修飾が難しいという難点が生じている。
    動物数を増やすとともに、シリコンシェルを平滑面にして同様に各種コーティングを行って同様に追跡し、シリコンシェル片の移動性や回転性をさらに調査する予定である。
    またシリコンシェル挿入後に生成された被膜を摘出して組織学的評価を行ったが、今後サンプル数を増やし実験の再現性を確認し、移植するシリコンの条件や留置期間を変えて調査を進めていく。
    これと並行して、医療用インプラントへのペプチド修飾を前提とした方法を検証を進めていく。

  3. 神経線維腫症1型の特性から解明するScarless Wound Healing

    Grant number:21K09763  2021.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    大石 真由美, 新城 恵子, 高成 啓介, 橋川 和信, 蛯沢 克己, 神戸 未来, 樋口 慎一, 山本 周平, 亀井 譲

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    本研究の目的は神経線維腫症1型(NF-1)の創傷治癒から瘢痕抑制のメカニズムを解明し、scarless wound healingを可能とする新規治療薬を開発することである。NF-1では手術後の瘢痕が目立ちにくく、肥厚性瘢痕やケロイドを生じにくいことが経験的に知られているが、NF-1の創傷治癒過程における過剰な瘢痕形成を抑制するメカニズムは明らかではない。現在行われている瘢痕治療の効果は限定的であり、手術や外傷後に傷あとが残ることは不可避であったが、NF-1に特有な創傷治癒メカニズムを再現することで、scarless wound healingの実現を試みる。
    本研究の目的は、NF-1における創傷治癒と瘢痕抑制のメカニズムを解明し、scarless wound healingを実現する新規治療薬を開発することである。
    昨年度までの実験では、正常な皮膚線維芽細胞に対するTGFβ-1の刺激によって筋線維芽細胞マーカーであるαSMA・TAGLNやⅠ型コラーゲンを構成するCOL1A2の発現上昇が確認された。しかし、NF-1患者由来の線維芽細胞では長期継代培養が安定して成功しなかったため当初の計画通りに研究を遂行することが困難であった。
    そこで、過剰な瘢痕を形成するケロイドの原因となる分子メカニズムを解明することが、scarless wound healingにも応用可能であると考え、研究の焦点をケロイドに変更した。
    まず、ケロイドおよび未熟瘢痕に対して免疫組織化学的染色を行い、筋線維芽細胞の分布を調べた。次に、ケロイドおよび未熟瘢痕の組織中で筋線維芽細胞が豊富な領域からトランスクリプトーム解析を行い、発現変動遺伝子を同定した。ケロイド特異的遺伝子として同定されたKANK4を線維芽細胞に過剰発現させ、細胞遊走アッセイを実施したところ、線維芽細胞の移動が促進された。
    これらの実験結果から、ケロイド組織では、高い移動能を示すKANK4陽性の筋線維芽細胞が元の創傷を越えて移動することでケロイド病変の拡大に寄与していると考えられた。KANK4はケロイド治療の新規ターゲットであると同時に、scarless wound healingの治療標的となる可能性が示唆された。
    当初予定していた研究計画に変更があったものの、その後の進捗は順調といえる。
    モデル動物の創傷内で筋線維芽細胞の分化抑制実験を行い、scarless wound healingに有用であるかどうかを検証する。