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LE Thi Hue
大学院医学系研究科 医療創成工学専攻
助教

研究者基本情報

■ 学位
  • 博士（医学）, 和歌山県立医科大学

研究活動情報

■ 受賞
  • 2024年05月 Best Poster Presentation Award at the 12th World Biomaterials Congress, Korea., Widely distributable boronic acid-based adhesive hydrogel for treating vascular graft stenosis and myocardial infarction
    Hue Thi Le, Tetsuji Yamaoka, Atsushi Mahara

  • 2023年12月 A nominee for the best poster award in 2023 MRS Fall Meeting and Exhibit, Boston-USA, Prevention of adverse ventricular remodeling post-myocardial infarction by sorbitol-responsive in-situ gelling material.
    Hue Thi Le, Atsushi Mahara, Takeshi Nagasaki, Tetsuji YAMAOKA

  • 2022年11月 第44回日本ビオマテリアル学会大会, ハイライト講演

  • 2020年11月 Third prize Dang Van Ngu award, Hanoi Medical University

  • 2020年03月 和歌山県立医科大学学位記授与式における医学研究科博士課程修了生代表者

  • 2019年07月 87回和歌山医学会, 若手プレゼンテーション賞

■ 論文
  • Atsushi Mahara, Kaito Shimizu, Hue Thi Le, Raghav Soni, Yoshiaki Hirano, Tetsuji Yamaoka
    Local vascular injury caused by vascular transplantation and endarterectomy causes intimal hyperplasia accompanied by matrix degradation by the matrix metalloproteinase (MMP) and proliferation of acute smooth muscle cells (SMCs) during the wound healing. In small vessels, excessive intimal thickening easily induces graft occlusion, and regulation of these local events is critical for graft patency. Although cilostazol (CLZ) has been investigated in clinical trials as a stenosis-suppressing medicine, strategies targeting the suppression of anastomotic stenosis are insufficient. In this study, we developed CLZ-loaded acellular grafts that respond to MMP using a reprecipitation process. CLZ weighing 112 μg was loaded into an acellular graft (CLZ-Graft) weighing 10 mg via reprecipitation. The loaded CLZ was gradually released via matrix degradation but did not leak without degradation. The SMC phenotype changed to a contracted type and proliferation was suppressed when the SMCs were cultured with the CLZ-Graft lysate. The lysate did not inhibit endothelial cell migration or vasculogenesis. In a rat carotid artery ablation model, the graft diameter decreased to 48 % under control conditions. When the CLZ-Graft was placed around the injured carotid artery in rats, acute stenosis was suppressed to only 31 % and 18 % at two and four weeks, respectively. These results indicated that intimal hyperplasia was effectively suppressed by the local release of CLZ from CLZ-Graft in response to MMP. These findings demonstrate that drug-releasing from the decellularized tissue that responds to MMP is an effective strategy for inhibiting vascular stenosis.
    2025年12月, Biomaterials advances, 177, 214433 - 214433, 英語, 国際誌
    研究論文（学術雑誌）

  • Hue Thi Le, Atsushi Mahara, Takeshi Nagasaki, Tetsuji Yamaoka
    Mesenchymal stem cells (MSCs) repair damaged myocardium by secreting biological factors and have shown only modest therapeutic efficacy in clinical trials. We recently developed a sorbitol-responsive in situ gelling material (SRG) solution, which increases viscosity by diffusing out pre-added sorbitol upon contact with heart tissue without external stimulation. Here, this study demonstrates that intramyocardial injection of MSC-loaded SRG (MSC/SRG) improves cardiac function and facilitates tissue repair following acute myocardial ischemia in rats, and the underlying mechanisms are elucidated. MSC/SRG is more effective than either MSC or SRG alone in preventing cardiac dysfunction and fibrotic remodeling while stimulating angiogenesis. The optimized SRG consists of 25 mg/mL boronic acid group-bearing polymer, 10 mg/mL polyvinyl alcohol, and 5 mg/mL sorbitol, which prolongs MSC survival and enhances their paracrine function in in vitro and in vivo assays. Sorbitol supplementation increases MSC proliferation, modulates cytokine secretion from MSCs in a concentration-dependent manner, and promotes angiogenesis in vitro. These findings suggest that the sorbitol in SRG supports MSC survival and enhances MSC paracrine activity. The SRG may facilitate the therapeutic potential of MSC and hydrogel-based interventions for myocardial ischemia.
    2025年08月, Journal of controlled release : official journal of the Controlled Release Society, 386, 114148 - 114148, 英語, 国際誌
    研究論文（学術雑誌）

  • Wei Zhang, Kyoko Fukazawa, Atsushi Mahara, Hue Thi Le, Raghav Soni, Tetsuji Yamaoka
    Expanded polytetrafluoroethylene (ePTFE) is a widely used material in diverse medical devices, particularly in the cardiovascular system, owing to its chemical stability and suitable mechanical properties. However, the chemical inertness makes surface modification difficult. In the present study, modification of ePTFE with a peptide was successfully achieved based on a unique photoreaction technique. We previously screened the hemocompatible peptide (HCP), histidine-glycine-glycine-valine-arginine-leucine-tyrosine (HGGVRLY), with high endothelial affinity and antiplatelet ability as modifying molecules. We synthesized a photoreactive peptide by combining a phenylazide group with the HCP, which was subsequently immobilized on the ePTFE surface through a short UV exposure time after argon plasma (Ar) treatment. Cross-sectional images of the surface modified with fluorescent-labeled photoreactive HCP showed efficient modification even within the pores of ePTFE. In vitro assessment revealed that modification improved the endothelial affinity of ePTFE approximately 5-fold while preventing platelet adhesion and aggregation. The ePTFE grafts were further implanted into an in situ porcine closed-circuit system for the blood contact assessment. Comparative investigations with untreated ePTFE grafts indicated that the modified ePTFE surface attracted more cells positive for CD14, CD16, CD34, and macrophage markers while concurrently exhibiting reduced platelet adhesion. In conclusion, photoreactive HCP proved to be a simple and effective strategy for modifying the ePTFE surface, resulting in enhanced hemocompatibility characterized by increased endothelial and monocyte recruitment as well as antiplatelet attachment on the modified ePTFE graft surface.
    2025年06月, ACS biomaterials science & engineering, 11(6) (6), 3467 - 3476, 英語, 国際誌
    研究論文（学術雑誌）

  • Atsushi Mahara, Satoki Ota, Hue Thi Le, Kaito Shimizu, Raghav Soni, Kentaro Kojima, Yoshiaki Hirano, Sachiro Kakinoki, Tetsuji Yamaoka
    Decellularized vascular tissue has high potential as a tissue-engineered vascular graft because of its similarity to native vessels in terms of mechanical strength. However, exposed collagen on the tissue induces blood coagulation, and low hemocompatibility is a major obstacle to its vascular application. Here we report that freeze-drying and ethanol treatment effectively modify collagen fiber structure and drastically reduce blood coagulation on the graft surface without exogenous chemical modification. Decellularized carotid artery of ostrich was treated with freeze-drying and ethanol solution at concentrations ranging between 5 and 99.5 %. Collagen fiber distance in the graft was narrowed by freeze-drying, and the non-helical region increased by ethanol treatment. Although in vitro blood coagulation pattern was similar on the grafts, platelet adhesion on the grafts was largely suppressed by freeze-drying and ethanol treatments. Ex vivo blood circulation tests also indicated that the adsorption of platelets and Von Willebrand Factor was largely reduced to approximately 80 % by ethanol treatment. These results indicate that structural modification of collagen fibers in decellularized tissue reduces blood coagulation on the surface by inhibiting platelet adhesion.
    2024年06月, International journal of biological macromolecules, 269(Pt 1) (Pt 1), 132040 - 132040, 英語, 国際誌
    研究論文（学術雑誌）

  • Hue Thi Le, Atsushi Mahara, Kyoko Fukazawa, Takeshi Nagasaki, Tetsuji Yamaoka
    Intramyocardial hydrogel injection is a promising therapy to prevent negative remodeling following myocardial infarction (MI). In this study, we report a mechanism for in-situ gel formation without external stimulation, resulting in an injectable and tissue-retainable hydrogel for MI treatment, and investigate its therapeutic outcomes. A liquid-like polymeric solution comprising poly(3-acrylamidophenylboronic acid-co-acrylamide) (BAAm), polyvinyl alcohol (PVA), and sorbitol (S) increases the viscous modulus by reducing the pre-added sorbitol concentration is developed. This solution achieves a sol-gel transition in-vitro in heart tissue by spontaneously diffusing the sorbitol. After intramyocardial injection, the BAAm/PVA/S with lower initial viscous modulus widely spreads in the myocardium and gelate compared to a viscoelastic alginate (ALG) hydrogel and is retained longer than the BAAm/S solution. Serial echocardiogram analyses prove that injecting the BAAm/PVA/S into the hearts of subacute MI rats significantly increases the fraction shortening and ejection shortening and attenuates the expansion of systolic LV diameter for up to 21 d after injection compared to the saline injection as a control, but the ALG injection does not. In addition, histological evaluation shows that only the BAAm/PVA/S decreases the infarct size and increases the wall thickness 21 d after injection. The BAAm/PVA/S intramyocardial injection is better at restraining systolic ventricular dilatation and cardiac failure in the rat MI model than in the control groups. Our findings highlight an effective injectable hydrogel therapy for MI by optimizing injectability-dependent distribution and retention of injected material. STATEMENT OF SIGNIFICANCE: In-situ gelling material is a promising strategy for intramyocardial hydrogel injection therapy for myocardial infarction (MI). Since the sol-gel transition of reported materials is driven by external stimulation such as temperature, pH, or ultraviolet, their application in vivo remains challenging. In this study, we first reported a synthetic in-situ gelling material (BAAm/PVA/S) whose gelation is stimulated by spontaneously reducing pre-added sorbitol after contacting the heart tissue. The BAAm/PVA/S solution spreads evenly, and is retained for at least 21 d in the heart tissue. Our study demonstrated that intramyocardial injection of the BAAm/PVA/S with more extensive distribution and longer retention had better effects on preventing LV dilation and improving cardiac function after MI than that of viscoelastic ALG and saline solution. We expect that these findings provide fundamental information for the optimum design of injectable biomaterials for treating MI.
    2024年01月, Acta biomaterialia, 176, 221 - 233, 英語, 国際誌
    研究論文（学術雑誌）

  • Atsushi Mahara, Manabu Shirai, Raghav Soni, Hue Thi Le, Kaito Shimizu, Yoshiaki Hirano, Tetsuji Yamaoka
    Although the clinical application of cell-free tissue-engineered vascular grafts (TEVGs) has been proposed, vascular tissue regeneration mechanisms have not been fully clarified. Here, we report that monocyte subpopulations reconstruct vascular-like tissues through integrin signaling. An Arg-Glu-Asp-Val peptide-modified acellular long-bypass graft was used as the TEVG, and tissue regeneration in the graft was evaluated using a cardiopulmonary pump system and porcine transplantation model. In 1 day, the luminal surface of the graft was covered with cells that expressed CD163, CD14, and CD16, which represented the monocyte subpopulation, and they exhibited proliferative and migratory abilities. RNA sequencing showed that captured cells had an immune-related phenotype similar to that of monocytes and strongly expressed cell adhesion-related genes. In vitro angiogenesis assay showed that tube formation of the captured cells occurred via integrin signal activation. After medium- and long-term graft transplantation, the captured cells infiltrated the tunica media layer and constructed vascular with a CD31/CD105-positive layer and an αSMA-positive structure after 3 months. This finding, including multiple early-time observations provides clear evidence that blood-circulating monocytes are directly involved in vascular remodeling.
    2023年12月, Materials today. Bio, 23, 100847 - 100847, 英語, 国際誌
    研究論文（学術雑誌）

  • Hue Thi Le, Atsushi Mahara, Takeshi Nagasaki, Tetsuji Yamaoka
    Abnormal proliferation of vascular smooth muscle cells (VSMCs) induces graft anastomotic stenosis, resulting in graft failure. Herein, we developed a drug-loaded tissue-adhesive hydrogel as artificial perivascular tissue to suppress VSMCs proliferation. Rapamycin (RPM), an anti-stenosis drug, is selected as the drug model. The hydrogel was composed of poly (3-acrylamidophenylboronic acid-co-acrylamide) (BAAm) and polyvinyl alcohol. Since phenylboronic acid reportedly binds to sialic acid of glycoproteins which is distributed on the tissues, the hydrogel is expected to be adherent to the vascular adventitia. Two hydrogels containing 25 or 50 mg/mL of BAAm (BAVA25 and BAVA50, respectively) were prepared. A decellularized vascular graft with a diameter of <2.5 mm was selected as a graft model. Lap-shear test indicates that both hydrogels adhered to the graft adventitia. In vitro release test indicated that 83 and 73 % of RPM in BAVA25 and BAVA50 hydrogels was released after 24 h, respectively. When VSMCs were cultured with RPM-loaded BAVA hydrogels, their proliferation was suppressed at an earlier stage in RPM-loaded BAVA25 hydrogels compared to RPM-loaded BAVA50 hydrogels. An in vivo preliminary test reveals that the graft coated with RPM-loaded BAVA25 hydrogel shows better graft patency for at least 180 d than the graft coated with RPM-loaded BAVA50 hydrogel or without hydrogel. Our results suggest that RPM-loaded BAVA25 hydrogel with tissue adhesive characteristics has potential to improve decellularized vascular graft patency.
    2023年04月, Biomaterials advances, 147, 213324 - 213324, 英語, 国際誌
    研究論文（学術雑誌）

  • Tsuyoshi Otsuka, Hue Thi Le, Zaw Lin Thein, Hayato Ihara, Fuyuki Sato, Tomomi Nakao, Akira Kohsaka
    Mood disorders such as depression, anxiety, and bipolar disorder are highly associated with disrupted daily rhythms of activity, which are often observed in shift work and sleep disturbance in humans. Recent studies have proposed the REV-ERBα protein as a key circadian nuclear receptor that links behavioural rhythms to mood regulation. However, how the Rev-erbα gene participates in the regulation of mood remains poorly understood. Here, we show that the regulation of the serotonergic (5-HTergic) system, which plays a central role in stress-induced mood behaviours, is markedly disrupted in Rev-erbα-/- mice. Rev-erbα-/- mice exhibit both negative and positive behavioural phenotypes, including anxiety-like and mania-like behaviours, when subjected to a stressful environment. Importantly, Rev-erbα-/- mice show a significant decrease in the expression of a gene that encodes the rate-limiting enzyme of serotonin (5-HT) synthesis in the raphe nuclei (RN). In addition, 5-HT levels in Rev-erbα-/- mice are significantly reduced in the prefrontal cortex, which receives strong inputs from the RN and controls stress-related behaviours. Our findings indicate that Rev-erbα plays an important role in controlling the 5-HTergic system and thus regulates mood and behaviour.
    2022年09月, Physiology & behavior, 256, 113960 - 113960, 英語, 国際誌
    研究論文（学術雑誌）

  • Xiaoyan Li, Hue Thi Le, Fuyuki Sato, Tong Ho Kang, Makoto Makishima, Liangjun Zhong, Yi Liu, Lijia Guo, Ujjal K Bhawal
    Cardiac inflammation and fibrosis triggered by left ventricular pressure overload are the major causes of heart dysfunction. Differentiated embryonic chondrocyte gene 1 (Dec1) is a basic helix-loop-helix transcription factor that is comprehensively involved in inflammation and tissue fibrosis, but its role in cardiac hypertrophy remains unclear. This study explored the effects of Dec1 on cardiac fibrosis, inflammation, and apoptosis in hypertrophic conditions. Transverse aortic constriction (TAC) was performed to induce cardiac hypertrophy in wild-type (WT) mice and in Dec1 knock out (KO) mice for 4 weeks. Using the TAC mouse model, prominent differences in cardiac hypertrophy at the morphological, functional, and molecular levels were delineated by Masson's Trichrome and TUNEL staining, immunohistochemistry, RT-PCR and Western Blot. DNA microarray and microRNA (miRNA) array analyses were carried out to identify gene and miRNA expression patterns. Dec1KO mice exhibited a more severe hypertrophic heart, whereas WT mice showed a more pronounced perivascular fibrosis after TAC at 4 weeks. The Dec1 deficiency promoted M2 phenotype macrophages. Dec1KO TAC mice showed fewer apoptotic cells than WT TAC mice. APEX1, WNT16, FGF10 and MMP-10 were differentially expressed according to DNA microarray analysis and expression levels of those genes and the corresponding miRNAs (miR-295, miR-200 b, miR-130a, miR-92a) showed the same trends. Furthermore, luciferase reporter assay confirmed that FGF10 is the direct target gene of miR-130. In conclusion, a Dec1 deficiency protects the heart from perivascular fibrosis, regulates M1/M2 macrophage polarization and reduces cell apoptosis, which may provide a novel insight for the treatment of cardiac hypertrophy.
    2020年11月, Biochemical and biophysical research communications, 532(4) (4), 513 - 519, 英語, 国際誌
    研究論文（学術雑誌）

  • Tsuyoshi Otsuka, Hue Thi Le, Akira Kohsaka, Fuyuki Sato, Hayato Ihara, Tomomi Nakao, Masanobu Maeda
    2020年04月, Neuroscience, 432, 44 - 54, 英語, 国際誌
    研究論文（学術雑誌）

  • Hue Thi Le, Fuyuki Sato, Akira Kohsaka, Ujjal K Bhawal, Tomomi Nakao, Yasuteru Muragaki, Masanori Nakata
    Cardiac fibrosis is a major cause of cardiac dysfunction in hypertrophic hearts. Differentiated embryonic chondrocyte gene 1 (Dec1), a basic helix-loop-helix transcription factor, has circadian expression in the heart; however, its role in cardiac diseases remains unknown. Therefore, using Dec1 knock-out (Dec1KO) and wild-type (WT) mice, we evaluated cardiac function and morphology at one and four weeks after transverse aortic constriction (TAC) or sham surgery. We found that Dec1KO mice retained cardiac function until four weeks after TAC. Dec1KO mice also revealed more severely hypertrophic hearts than WT mice at four weeks after TAC, whereas no significant change was observed at one week. An increase in Dec1 expression was found in myocardial and stromal cells of TAC-treated WT mice. In addition, Dec1 circadian expression was disrupted in the heart of TAC-treated WT mice. Cardiac perivascular fibrosis was suppressed in TAC-treated Dec1KO mice, with positive immunostaining of S100 calcium binding protein A4 (S100A4), alpha smooth muscle actin (αSMA), transforming growth factor beta 1 (TGFβ1), phosphorylation of Smad family member 3 (pSmad3), tumor necrosis factor alpha (TNFα), and cyclin-interacting protein 1 (p21). Furthermore, Dec1 expression was increased in myocardial hypertrophy and myocardial infarction of autopsy cases. Taken together, our results indicate that Dec1 deficiency suppresses cardiac fibrosis, preserving cardiac function in hypertrophic hearts. We suggest that Dec1 could be a new therapeutic target in cardiac fibrosis.
    2019年10月, International journal of molecular sciences, 20(19) (19), 英語, 国際誌
    研究論文（学術雑誌）

  • Fuyuki Sato, Tsuyoshi Otsuka, Akira Kohsaka, Hue Thi Le, Ujjal K Bhawal, Yasuteru Muragaki
    Smad3 has circadian expression; however, whether Smad3 affects the expression of clock genes is poorly understood. Here, we investigated the regulatory mechanisms between Smad3 and the clock genes Dec1, Dec2, and Per1. In Smad3 knockout mice, the amplitude of locomotor activity was decreased, and Dec1 expression was decreased in the suprachiasmatic nucleus, liver, kidney, and tongue compared with control mice. Conversely, Dec2 and Per1 expression was increased compared with that of control mice. In Smad3 knockout mice, immunohistochemical staining revealed that Dec1 expression decreased, whereas Dec2 and Per1 expression increased in the endothelial cells of the kidney and liver. In NIH3T3 cells, Smad3 overexpression increased Dec1 expression, but decreased Dec2 and Per1 expression. In a wound-healing experiment that used Smad3 knockout mice, Dec1 expression decreased in the basal cells of squamous epithelium, promoting wound healing of the mucosa. Finally, the migration and proliferation of Smad3 knockdown squamous carcinoma cells was suppressed by Dec1 overexpression but was promoted by Dec2 overexpression. Dec1 overexpression decreased E-cadherin and proliferating cell nuclear antigen expression, whereas these expression levels were increased by Dec2 overexpression. These results suggest Smad3 is relevant to circadian rhythm and regulates cell migration and proliferation through Dec1, Dec2, and Per1 expression.
    2019年04月, The American journal of pathology, 189(4) (4), 773 - 783, 英語, 国際誌
    研究論文（学術雑誌）

  • Tomomi Nakao, Akira Kohsaka, Tsuyoshi Otsuka, Zaw Lin Thein, Hue Thi Le, Hidefumi Waki, Sabine S Gouraud, Hayato Ihara, Masako Nakanishi, Fuyuki Sato, Yasuteru Muragaki, Masanobu Maeda
    The daily rhythm of glucose metabolism is governed by the circadian clock, which consists of cell-autonomous clock machineries residing in nearly every tissue in the body. Disruption of these clock machineries either environmentally or genetically induces the dysregulation of glucose metabolism. Although the roles of clock machineries in the regulation of glucose metabolism have been uncovered in major metabolic tissues, such as the pancreas, liver, and skeletal muscle, it remains unknown whether clock function in non-major metabolic tissues also affects systemic glucose metabolism. Here, we tested the hypothesis that disruption of the clock machinery in the heart might also affect systemic glucose metabolism, because heart function is known to be associated with glucose tolerance. We examined glucose and insulin tolerance as well as heart phenotypes in mice with heart-specific deletion of Bmal1, a core clock gene. Bmal1 deletion in the heart not only decreased heart function but also led to systemic insulin resistance. Moreover, hyperglycemia was induced with age. Furthermore, heart-specific Bmal1-deficient mice exhibited decreased insulin-induced phosphorylation of Akt in the liver, thus indicating that Bmal1 deletion in the heart causes hepatic insulin resistance. Our findings revealed an unexpected effect of the function of clock machinery in a non-major metabolic tissue, the heart, on systemic glucose metabolism in mammals.
    2018年04月, Chronobiology international, 35(4) (4), 499 - 510, 英語, 国際誌
    研究論文（学術雑誌）

■ MISC
  • 金ナノ粒子を内包したヒアルロン酸ナノ自己集合体の調製
    松本真歩, 犬伏祥子, 國久智成, 谷野裕一, 下田麻子, 秋吉一成, HUE Le Thi, 大谷亨, 大谷亨
    2025年, 日本バイオマテリアル学会大会予稿集(Web), 47th

  • 光線力学療法への応用を目指した水溶性光増感剤の合成
    松山大毅, 宮原蒼月, 南埜早紀, 和田百世, 川内敬子, 三好大輔, HUE Le Thi, 大谷亨, 大谷亨, 大谷亨, 大谷亨
    2025年, 日本バイオマテリアル学会大会予稿集(Web), 47th

  • 医療用ロボットスキンへの応用を目指した超分子レジン調製法の検討
    河合胡春, HUE Le Thi, 大谷亨, 大谷亨
    2025年, 日本バイオマテリアル学会大会予稿集(Web), 47th

  • グリコールキトサンとポリオールの組合せによって引き起こされる迅速なゲル化現象【JST機械翻訳】|||
    HUE Le Thi, KAWASAKI Shiho, OOYA Tooru
    2025年, 日本バイオマテリアル学会大会予稿集(Web), 47th

  • PEG修飾ヒアルロン酸の酵素分解特性の解析:ヒアルロン酸による血管新生へ向けて
    縄田実優, 橋本美優, THI HUE Le, 大谷亨
    2025年, 日本バイオマテリアル学会大会予稿集(Web), 47th

  • シロスタゾール含有脱細胞血管の作製とin vivo評価
    馬原淳, LE Hue, SONI Raghav, 山岡哲二
    2024年, 人工臓器(日本人工臓器学会), 53(2) (2)

  • 心筋梗塞におけるMSC移植のためのボロン酸ベース接着剤注入可能ヒドロゲル【JST機械翻訳】|||
    LE THI Hue
    2024年, 日本再生医療学会総会(Web), 23rd

  • コラーゲンの立体構造修飾による脱細胞組織の抗血栓性化
    馬原淳, LE Hue, 清水開斗, 清水開斗, SONI Raghav, 平野義明, 山岡哲二, 山岡哲二
    2024年, 日本再生医療学会総会(Web), 23rd

  • 単球細胞が関与するペプチド修飾脱細胞血管の内皮化機序
    馬原 淳, Le Thi Hue, 清水 開斗, Raghav Soni, 平野 義明, 山岡 哲二
    (一社)日本人工臓器学会, 2023年06月, 人工臓器, 52(1) (1), 42 - 42, 日本語

  • 【バイオマテリアル研究を担う若手研究者たち3】心血管病に対するヒドロゲル注射による新規治療法の開発の取り組み(Challenges of new therapeutic applications for cardiovascular diseases by hydrogel injection)
    レ・ティ・フォエ, 馬原 淳, 深澤 今日子, 山岡 哲二
    日本バイオマテリアル学会, 2023年04月, バイオマテリアル-生体材料-, 41(2) (2), 117 - 120, 英語

  • バイオマテリアル研究を担う若手研究者たち3 ヒドロゲル注射による心血管疾患の新規治療の課題
    LE Hue Thi, MAHARA Atsushi, FUKAZAWA Kyoko, YAMAOKA Tetsuji
    2023年, バイオマテリアル(Web), 41(2) (2)

  • 脱細胞血管組織のマトリックス構造による血液凝固反応の制御
    馬原淳, LE Hue Thi, 清水開斗, 清水開斗, SONI Raghav, 平野義明, 平野義明, 山岡哲二, 山岡哲二
    日本バイオマテリアル学会, 2023年, 日本バイオマテリアル学会大会予稿集(Web), 45th, 128 - 128, 日本語

  • ソルビトール応答性in situ形成ヒドロゲルは心筋梗塞後の心室拡張を予防する【JST・京大機械翻訳】|||
    LE Hue Thi, NAGASAKI Takeshi, YAMAOKA Tetsuji, YAMAOKA Tetsuji, MAHARA Atsushi
    2023年, 日本バイオマテリアル学会大会予稿集(Web), 45th

  • 薬剤徐放型脱細胞組織による人工血管吻合部での狭窄制御
    清水開斗, 清水開斗, LE Hue Thi, 平野義明, 平野義明, 山岡哲二, 山岡哲二, 馬原淳
    2023年, 日本バイオマテリアル学会大会予稿集(Web), 45th

  • 単核球細胞が関与する組織再生誘導型小口径脱細胞血管の内膜形成
    馬原淳, HUE Le, 清水開斗, 清水開斗, RAGHAV Soni, 平野義明, 山岡哲二
    2023年, 日本再生医療学会総会(Web), 22nd

  • 心筋虚血の治療を目指したsorbitol self-releasing injectable hydrogel(Sorbitol self-releasing injectable hydrogel for the treatment of myocardial ischemia)
    Le Thi Hue, Fukazawa Kyoko, Mahara Atsushi, Nagasaki Takeshi, Yamaoka Tetsuji
    日本バイオマテリアル学会, 2022年11月, 日本バイオマテリアル学会大会予稿集, 44回, 154 - 154, 英語

  • 単核球細胞による組織再生型小口径人工血管の組織再生メカニズム
    馬原 淳, レ・ティ・フォエ, 清水 開斗, ソニ・ラグハブ, 平野 義明, 山岡 哲二
    日本バイオマテリアル学会, 2022年11月, 日本バイオマテリアル学会大会予稿集, 44回, 139 - 139, 日本語

  • 次世代の人工臓器を実現するためのテクノロジー 単球細胞が関与するペプチド修飾脱細胞血管の内皮化機序
    馬原 淳, レ・フォエ, 清水 開斗, ソニ・ラグハブ, 平野 義明, 山岡 哲二
    (一社)日本人工臓器学会, 2022年10月, 人工臓器, 51(2) (2), S - 34, 日本語

  • 脱細胞化組織の事業化に向けた研究開発・非臨床・臨床試験と展望 食用ダチョウの頸動脈を材料とした脱細胞化小口径血管の非臨床POCおよび治験計画
    山岡 哲二, 山本 敬史, 馬原 淳, 山中 浩気, Le Thi Hue, 小川 興, 井手 純一, 森本 尚樹
    (一社)日本人工臓器学会, 2022年10月, 人工臓器, 51(2) (2), S - 39, 日本語

  • 単球細胞が関与するペプチド修飾脱細胞血管の内皮化機序
    馬原 淳, レ・フォエ, 清水 開斗, ソニ・ラグハブ, 平野 義明, 山岡 哲二
    (一社)日本人工臓器学会, 2022年10月, 人工臓器, 51(2) (2), S - 127, 日本語

  • 組織表面で皮膜を形成する新たなバオマテリアルメカニズム-癒着防止・止血・創傷被覆・組織接着のために-
    山岡哲二, 松井直, 松井直, LE Hue, 長崎健, 深澤今日子
    2022年, 日本形成外科学会基礎学術集会プログラム・抄録集, 31st

  • 脱細胞化異種小口径人工血管の実用化研究
    山本敬史, 山岡哲二, 馬原淳, 山中浩気, HUE Le Thi, 井手純一, 西原愛美, 小川興, 小川興, 森本尚樹
    2022年, 日本形成外科学会基礎学術集会プログラム・抄録集, 31st

  • 心筋梗塞を治療するためのソルビトール応答性の注射用ヒドロゲルの開発
    LE Hue Thi, FUKAZAWA Kyoko, MATSUI Sunao, MATSUI Sunao, NAGASAKI Takeshi, MAHARA Atsushi, YAMAOKA Tetsuji
    日本バイオマテリアル学会, 2021年11月, 日本バイオマテリアル学会大会予稿集(Web), 43回, AP2 - 15, 英語

  • 血液細胞によるペプチド修飾脱細胞血管の組織再生
    馬原 淳, Hue Le Thi, 山岡 哲二
    日本バイオマテリアル学会, 2021年11月, 日本バイオマテリアル学会大会予稿集, 43回, JO - 1C02, 日本語

  • ペプチド修飾脱細胞血管の内腔で捕捉される血中循環細胞の評価
    馬原淳, ティ フォエレ, 山岡哲二
    2021年, 人工臓器(日本人工臓器学会), 50(2) (2)

  • Le Thi Hue, Kohsaka Akira, Nakao Tomomi, Nakata Masanori, Sato Fuyuki, Muragaki Yasuteru
    和歌山医学会, 2019年12月, 和歌山医学, 70(4) (4), 180 - 180, 英語

  • 生体リズムの乱れは情動行動および前頭前皮質の時計遺伝子機能に影響する
    向阪 彰, 大塚 剛司, レ・ティ・フォエ, 中田 正範
    和歌山医学会, 2018年12月, 和歌山医学, 69(4) (4), 199 - 199, 日本語

  • Rev-erba不足がマウスのserotonin作動系と気分調節に及ぼす影響(Effects of Rev-erbαdeficiency on the serotonergic system and mood regulation in mice)
    Otsuka Tsuyoshi, Kohsaka Akira, Le Thi Hue, Nakao Tomomi, Thein Lin Zow, Maeda Masanobu
    (一社)日本生理学会, 2018年03月, The Journal of Physiological Sciences, 68(Suppl.1) (Suppl.1), S130 - S130, 英語

  • ストレス下の食事摂取量調節における概日性の転写抑制因子REV-ERBαの役割(Role of the circadian transcriptional repressor, REV-ERBα, in the regulation of food intake under stress)
    Thein Lin Zaw, Kohsaka Akira, Otsuka Tsuyoshi, Tsujimoto Takayuki, Le Thi Hue, Nakao Tomomi, Maeda Masanobu
    (一社)日本生理学会, 2018年03月, The Journal of Physiological Sciences, 68(Suppl.1) (Suppl.1), S159 - S159, 英語

  • 心臓特異的な時計遺伝子Bmal1の欠損は肝臓のインスリン抵抗性を惹起する
    中尾 友美, 向阪 彰, レティ・フォエ, 大塚 剛司, テン・ソーレン, 佐藤 冬樹, 井原 勇人, 前田 正信
    (一社)日本内分泌学会, 2017年04月, 日本内分泌学会雑誌, 93(1) (1), 269 - 269, 日本語

  • 情動行動制御における前頭前皮質の時計遺伝子Rev-erbαの役割(Transcriptome analysis reveals dysregulation of the prefrontal neuronal networks of Reverbα deficient mice)
    Otsuka Tsuyoshi, Kohsaka Akira, Le Hue Thi, Nakao Tomomi, Thien Zaw Lin, Maeda Masanobu
    (一社)日本生理学会, 2017年03月, The Journal of Physiological Sciences, 67(Suppl.1) (Suppl.1), S165 - S165, 英語

  • 概日リズムの同期障害はマウス前頭前野の気分と神経活動に関連する遺伝子の調節を変化させる(Circadian desynchronization alters mood and the regulation of genes associated with neuronal activity in the prefrontal cortex of mice)
    Le Hue Thi, Otsuka Tsuyoshi, Kohsaka Akira, Nakao Tomomi, Thien Zaw Lin, Maeda Masanobu
    (一社)日本生理学会, 2017年03月, The Journal of Physiological Sciences, 67(Suppl.1) (Suppl.1), S165 - S165, 英語

  • トランスクリプトーム解析を用いた時計遺伝子による心筋ミトコンドリア調節機構の解明(Transcriptome analysis reveals regulatory networks linking the clock and heart mitochondrial function in mice)
    Nakao Tomomi, Kohsaka Akira, Le Hue Thi, Otsuka Tsuyoshi, Thein Zaw Lin, Sato Fuyuki, Ihara Hayato, Maeda Masanobu
    (一社)日本生理学会, 2017年03月, The Journal of Physiological Sciences, 67(Suppl.1) (Suppl.1), S165 - S165, 英語

  • マウスの情動行動制御における時計遺伝子Rev-erb αの役割
    大塚 剛司, 向阪 彰, Le Thi Hue, 前田 正信
    (公社)日本畜産学会, 2016年03月, 日本畜産学会大会講演要旨集, 121回, 202 - 202, 日本語

  • 情動行動異常を伴う時計遺伝子Rev-erbα KOマウスにおける脳部位特異的な遺伝子発現パターンの解析
    大塚剛司, 向阪彰, レティ フォエ, 前田正信
    2016年, 日本生理学雑誌(Web), 78(1) (1)

  • 心臓の分子時計異常が与える全身の糖代謝調節への影響
    中尾 友美, 向阪 彰, 大塚 剛司, レ・ティフォエ, 前田 正信
    (一社)日本生理学会, 2016年01月, 日本生理学雑誌, 78(1) (1), 22 - 22, 日本語

  • 時計遺伝子Rev-erbαの機能異常による体温調節障害
    小形 光, 向阪 彰, 大塚 剛司, レ・ティフォエ, 前田 正信
    (一社)日本生理学会, 2016年01月, 日本生理学雑誌, 78(1) (1), 22 - 22, 日本語

  • マウス心筋の体内時計異常はインスリン抵抗性を引き起こす
    向阪彰, 中尾友美, 大塚剛司, レ ティ フォエ, 前田正信
    2015年, 高血圧関連疾患モデル学会学術総会抄録集, 51st

■ 共同研究・競争的資金等の研究課題
  • An smart three-layer vascular graft with endothelial guidance and on-demand immunomodulation for long-term patency
    Le Thi.Hue
    日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2026年04月01日 - 2029年03月31日

  • A new vascular regenerative therapy for myocardial ischemia using intergin-specific circulating monocytes
    Le Thi.Hue
    日本学術振興会, 科学研究費助成事業, 若手研究, 国立研究開発法人国立循環器病研究センター, 2024年04月01日 - 2027年03月31日

  • 超分子MRプローブで挑む脳腫瘍微細血管形成の４次元ライブイメージング
    馬原 淳, Soni Raghav, 齋藤 茂芳, Le Thi.Hue
    日本学術振興会, 科学研究費助成事業, 基盤研究(B), 国立研究開発法人国立循環器病研究センター, 2024年04月01日 - 2026年03月31日
    本研究は、脳組織全体を対象として微細血管構造を“単一個体”、“長期”、“インビボ”、“生きたまま”、”全組織“、”高精細“で可視化できるMRイメージング技術を確立し、原発性脳腫瘍の増大に伴う微細血管構造の形成を空間・時間情報を含む４次元ライブイメージングで可視化することを目的とする。超分子構造体を形成する高分子化合物をMRプローブとして用いて、10 μmの解像度で脳微細血管イメージングできる超分子構造体形成型MRプローブを開発し、従来法ではライブイメージングできなかった脳腫瘍増大に伴う微細血管形成の４次元ライブイメージングに挑戦する。 令和６年度では、微細血管構造をより鮮明に描出できるプローブの分子設計として、従来までのフルオレセイン結合PEGのみならず、他の芳香族系色素を結合させた分子を合成し、DLS、血中滞留性評価、ならびにMRIによる造影効果の予備的検討を進めた。その結果、選択した特定の蛍光色素において、フルオレセインよりも低濃度で安定に超分子構造体を形成できる構造体を見出した。これにより、投与量を減らして微細血管を鮮明に描出できる可能性が見いだせた。 また腫瘍モデルにおけるライブイメージングに関しては、手術手技が簡便である皮下移植モデルを用いて、イメージングデータ取得条件や造影剤投与スケジュールを評価した。T1W, T2Wイメージ、ならびに超分子構造の造影剤投与後のMRA撮像、その後の低分子造影剤投与、の組み合わせにより腫瘍部位の同定と、腫瘍内部における微細血管構造を描出することに成功した。また、血管が成長する様子や、がん細胞特有の微細血管構造の形成をＭＲで追跡することができ、成果の一部は論文投稿を完了した。

  • 超分子MRプローブで挑む脳腫瘍微細血管形成の４次元ライブイメージング
    馬原 淳, Soni Raghav, 齋藤 茂芳, Le Thi.Hue
    日本学術振興会, 科学研究費助成事業, 基盤研究(B), 国立研究開発法人国立循環器病研究センター, 2023年04月01日 - 2026年03月31日

  • A new glucose-responsive injectable hydrogel for mesenchymal stem cells transplantation to rat myocardial infarction heart
    Le Thi.Hue
    日本学術振興会, 科学研究費助成事業, 研究活動スタート支援, 国立研究開発法人国立循環器病研究センター, 2021年08月30日 - 2023年03月31日
    The difficulty in the delivery of mesenchymal stem cells (MSCs) to the heart tissue limit MSC’s efficacy in the treatment of myocardial infarction. To overcome this limitation, this study is developing a proof of concept for the glucose-responsive injectable hydrogel whose sol-gel transition depends on sorbitol or glucose concentration to elongate of MSCs retention in the heart and improve the function of the myocardial infarction (MI) heart. Firstly, the injectable hydrogel was prepared and its potential for self-release of sorbitol/glucose was demonstrated by measuring changes in glucose/sorbitol concentration and viscoelasticity of glucose/sorbitol-responsive hydrogel in contact with porcine heart tissue time up to 60 minutes. Also, the characterization of MSCs isolated from rat adipose tissue as well as the cell viability in culturing with the hydrogel was assessed. To reduce the viscosity and improve the injectable potential of the hydrogel, sorbitol was chosen instead of glucose. The hydrogel containing sorbitol was then injected into the rat MI hearts and its effects in improving cardiac function and suppressing cardiac fibrosis in rat myocardial infarction were observed. These results were presented at the 8th Asian Biomaterial Congress and the 2022 USA-Japan joint Biomaterial symposium

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