研究者詳細 - 寳田　剛志

論文 - 寳田　剛志

分割表示 169 件中 1 - 20 件目／全件表示 >>

SGCRNA: Spectral Clustering-Guided Co-Expression Network Analysis Without Scale-Free Constraints for Multi-Omic Data

Tatsunori Osone, Tomoka Takao, Shigeo Otake, Takeshi Takarada

bioRxiv 2025年4月

Modeling human limb skeletal development using human pluripotent stem cell-derived skeletal assembloids

Tomoka Takao, Tatsunori Osone, Kohei Sato, Daisuke Yamada, Yuki Fujisawa, Masaya Hagiwara, Eiji Nakata, Toshifumi Ozaki, Junya Toguchida, Takeshi Takarada

bioRxiv 2025年1月

PRRX1 upregulates PD-L1 in human mesenchymal stem cells

Taro Osawa, Daisuke Yamada, Tomoko Takao, Lu Ming, Takeshi Takarada

In Vitro Cellular & Developmental Biology - Animal 2024年12月

Efficient Production of Chondrocyte Particles from Human iPSC-Derived Chondroprogenitors Using a Plate-Based Cell Self-Aggregation Technique. 国際誌

Shojiro Hanaki, Daisuke Yamada, Tomoka Takao, Ryosuke Iwai, Takeshi Takarada

International journal of molecular sciences 25 ( 22 ) 2024年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

The limited capacity of articular cartilage for self-repair is a critical challenge in orthopedic medicine. Here, we aimed to develop a simplified method of generating chondrocyte particles from human-induced pluripotent stem cell-derived expandable limb-bud mesenchymal cells (ExpLBM) using a cell self-aggregation technique (CAT). ExpLBM cells were induced to form chondrocyte particles through a stepwise differentiation protocol performed on a CAT plate (prevelex-CAT®), which enables efficient and consistent production of an arbitrary number of uniformly sized particles. Histological and immunohistochemical analyses confirmed that the generated chondrocyte particles expressed key cartilage markers, such as type II collagen and aggrecan, but not hypertrophic markers, such as type X collagen. Additionally, when these particles were transplanted into osteochondral defects in rats with X-linked severe combined immunodeficiency, they demonstrated successful engraftment and extracellular matrix production, as evidenced by Safranin O and Toluidine Blue staining. These data suggest that the plate-based CAT system offers a robust and scalable approach to produce a large number of chondrocyte particles in a simplified and efficient manner, with potential application to cartilage regeneration. Future studies will focus on refining the system and exploring its clinical applications to the treatment of cartilage defects.

DOI： 10.3390/ijms252212063

PubMed

researchmap

悪性末梢神経鞘腫瘍における悪性化を促進する新規メカニズム転写因子PRRX1とTOP2Aのタンパク質間相互作用の発見

たき平将太, 山田大祐, 大曽根達則, 高尾知佳, 板野拓人, 藤原智洋, 中田英二, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 98 ( 8 ) S1957 - S1957 2024年9月

悪性末梢神経鞘腫瘍におけるPRRX1とTOP2Aの相互作用による悪性化メカニズムの新規解明

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 6 ) S1529 - S1529 2024年6月

ヒトiPS細胞由来軟骨組織を利用した小児気管疾患に対する再生治療法の開発

花木祥二朗, 高尾知佳, 藤澤佑樹, 山田大祐, 岩井良輔, 宝田剛志

日本小児外科学会雑誌 60 ( 3 ) 509 - 509 2024年4月

ヒトiPS細胞由来軟骨組織を利用した小児気管疾患に対する再生治療法の開発

花木祥二朗, 高尾知佳, 藤澤佑樹, 山田大祐, 岩井良輔, 宝田剛志

日本小児外科学会雑誌 60 ( 3 ) 509 - 509 2024年4月

PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours. 国際誌

Shota Takihira, Daisuke Yamada, Tatsunori Osone, Tomoka Takao, Masakiyo Sakaguchi, Michiyuki Hakozaki, Takuto Itano, Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Toshifumi Ozaki, Takeshi Takarada

British journal of cancer 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Paired related-homeobox 1 (PRRX1) is a transcription factor in the regulation of developmental morphogenetic processes. There is growing evidence that PRRX1 is highly expressed in certain cancers and is critically involved in human survival prognosis. However, the molecular mechanism of PRRX1 in cancer malignancy remains to be elucidated. METHODS: PRRX1 expression in human Malignant peripheral nerve sheath tumours (MPNSTs) samples was detected immunohistochemically to evaluate survival prognosis. MPNST models with PRRX1 gene knockdown or overexpression were constructed in vitro and the phenotype of MPNST cells was evaluated. Bioinformatics analysis combined with co-immunoprecipitation, mass spectrometry, RNA-seq and structural prediction were used to identify proteins interacting with PRRX1. RESULTS: High expression of PRRX1 was associated with a poor prognosis for MPNST. PRRX1 knockdown suppressed the tumorigenic potential. PRRX1 overexpressed in MPNSTs directly interacts with topoisomerase 2 A (TOP2A) to cooperatively promote epithelial-mesenchymal transition and increase expression of tumour malignancy-related gene sets including mTORC1, KRAS and SRC signalling pathways. Etoposide, a TOP2A inhibitor used in the treatment of MPNST, may exhibit one of its anticancer effects by inhibiting the PRRX1-TOP2A interaction. CONCLUSION: Targeting the PRRX1-TOP2A interaction in malignant tumours with high PRRX1 expression might provide a novel tumour-selective therapeutic strategy.

DOI： 10.1038/s41416-024-02632-8

PubMed

researchmap

悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024年3月

悪性末梢神経鞘腫瘍において転写因子PRRX1はTOP2Aと相互作用し悪性化を促進させる

たき平将太, 中田英二, 板野拓人, 藤原智洋, 国定俊之, 大曽根達則, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 98 ( 2 ) S76 - S76 2024年3月

神経線維腫症1型患者由来ヒトiPS細胞株の樹立

大澤太郎, 中田英二, 岡本真幸, 山田大祐, 二川摩周, 高尾知佳, 平沢晃, 尾崎敏文, 宝田剛志

日本レックリングハウゼン病学会学術大会プログラム・抄録集 15回 24 - 24 2024年2月

Antitumor activity of α-pinene in T-cell tumors. 国際誌

Masaya Abe, Noboru Asada, Maiko Kimura, Chie Fukui, Daisuke Yamada, Ziyi Wang, Masayuki Miyake, Takeshi Takarada, Mitsuaki Ono, Michinori Aoe, Wataru Kitamura, Masayuki Matsuda, Takashi Moriyama, Akifumi Matsumura, Yoshinobu Maeda

Cancer science 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.

DOI： 10.1111/cas.16086

PubMed

researchmap

ヒトiPS細胞由来肢芽間葉系細胞から作製した軟骨組織体を用いた骨再生

中田英二, 佐藤浩平, 高尾知佳, 藤澤祐樹, 山田大祐, 上原健敬, 藤原智洋, 尾崎敏文, 宝田剛志

移植 58 ( 3 ) 293 - 293 2023年12月

Alpha-Pinene As a Novel Therapeutic Agent for T-Cell Tumors

Blood 142 ( Supplement 1 ) 1441 - 1441 2023年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：American Society of Hematology

T-cell acute leukemia and lymphoma have poor prognoses, necessitating the development of novel therapeutic agents. In this study, we investigated the antitumor activity of α-pinene, a monoterpene compound, against T-cell tumors. We evaluated the effects of α-pinene on cell growth inhibition in vitro using the murine T-cell tumor cell line EL-4 and the human-derived T-cell tumor cell line Molt-4. In addition, we assessed the effects of limonene, another monoterpene with reported tumor-suppressive effects, as a comparative agent.

Both α-pinene and limonene demonstrated concentration- and time-dependent inhibition of cell growth in both the EL-4 and Molt-4 cell lines (Figure 1). Moreover, α-pinene exhibited greater potency than limonene in inhibiting the growth of various hematologic malignancies. Importantly, α-pinene and limonene had minimal effects on the growth of normal murine spleen T cells. Further investigation of the mechanisms of action of α-pinene revealed its ability to induce apoptosis and cell cycle arrest in EL-4 and Molt-4 cells. Transcriptomic profiling of α-pinene-treated EL-4 cells using RNA-seq identified differentially expressed genes associated with cellular damage and mitochondrial dysfunction. Increased intracellular ROS levels and mitochondrial impairment were observed in the T-cell tumors treated with α-pinene. The activation of intrinsic apoptotic pathways involving EGR1, p53, BCL-2, and BAX was found to contribute to α-pinene-induced apoptosis in T-cell tumors. Moreover, α-pinene inhibited the NF-κB signaling pathway, resulting in the reduced nuclear translocation of NF-κB p65 and decreased total intracellular NF-κB p65 levels in EL-4 cells. Additionally, we discovered that α-pinene induced ferroptosis, a newly identified programmed cell death process, in EL-4 cells through lipid peroxidation and iron accumulation. Activation of the system x c−/GSH/GPX4 axis and upregulation of iron transporters, such as Slc39a8 and TfR1, were observed in α-pinene-induced ferroptosis. Treatment with the ferroptosis inhibitor Fer-1 partially reversed the tumor-inhibiting effect of α-pinene in EL-4 cells. Finally, we administrated α-pinene to mice subcutaneously injected with luciferase-expressing EL-4 to evaluate the efficacy of α-pinene in vivo. The tumor growth was significantly inhibited by α-pinene treatment (vehicle: 1055 ± 101 mm 3; α-pinene: 701 ± 82 mm 3, p &lt; 0.01, Figure 2) without adverse effects on body weight or behavior. Immunohistochemistry analyses revealed a significant increase of CD8 + T-cells (vehicle: 8.1 ± 2.7 cells / field of view; α-pinene: 43.1 ± 12.2 cells / field of view , p &lt; 0.05) and NK1.1 + cells (vehicle: 5.1 ± 1.0 cells / field of view ; α-pinene: 41.1 ± 9.8 cells / field of view , p &lt; 0.01) in the tumors, suggesting that α-pinene may have an indirect antitumor effect by recruiting immune cells into tumors.

Overall, our findings demonstrate the antitumor activity of α-pinene against T-cell tumors through the induction of apoptosis, cell cycle arrest, and ferroptosis. α-Pinene shows promise as a potential therapeutic agent for T-cell tumors and warrants further investigation for its clinical application.

DOI： 10.1182/blood-2023-181447

researchmap

Development of cartilage tissue using a stirred bioreactor and human iPSC-derived limb bud mesenchymal cells. 国際誌

Yuki Fujisawa, Tomoka Takao, Daisuke Yamada, Takeshi Takarada

Biochemical and biophysical research communications 687 149146 - 149146 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Production of cartilaginous particles for regenerative medicine requires a large supply of chondrocytes and development of suitable production techniques. Previously, we successfully produced human induced pluripotent stem cell (hiPSC)-derived limb bud mesenchymal cells (ExpLBM cells) with a high chondrogenic differentiation potential that stably proliferate. It may be possible to use these cells in combination with a stirred bioreactor to develop a tissue-engineered cell culture technology with potential for scale-up to facilitate production of large amounts of cartilaginous particles. ExpLBM cells derived from 414C2 and Ff-I 14s04 (human leukocyte antigen homozygous) hiPSCs were seeded into a stirred bioreactor containing cartilage induction medium. To characterize the cartilaginous particles produced, we performed real-time quantitative reverse transcription-polymerase chain reaction and histological analyses. Additionally, we transplanted the cartilage tissue into osteochondral defects of immunocompromised rats to assess its functionality, and evaluated engraftment of the grafted tissue. We successfully produced large amounts of cartilaginous particles via cartilage induction culture in a stirred bioreactor. This tissue exhibited significantly increased expression levels of type II collagen (COL2), aggrecan (ACAN), and SRY-box transcription factor 9 (SOX9), as well as positive Safranin O and Toluidine blue staining, indicating that it possesses characteristics of hyaline cartilage. Furthermore, engrafted tissues in osteochondral knee defects of immunodeficient rats were positively stained for human vimentin, COL2, and ACAN as well as with Safranin O. In this study, we successfully generated large amounts of hiPSC-derived cartilaginous particles using a combination of tissue engineering techniques. This method is promising as a cartilage regeneration technology with potential for scale-up.

DOI： 10.1016/j.bbrc.2023.149146

PubMed

researchmap

Fabrication of shape-designable cartilage from human induced pluripotent stem cell-derived chondroprogenitors using a cell self-aggregation technique. 国際誌

Tomoyuki Ota, Tomoka Takao, Ryosuke Iwai, Takeshi Moriwaki, Yohei Kitaguchi, Yuki Fujisawa, Daisuke Yamada, Yoshihiro Kimata, Takeshi Takarada

Biomedical materials (Bristol, England) 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

With the advancement of tissue engineering technologies, implantable materials have been developed for use in facial plastic surgery, including auriculoplasty and rhinoplasty. Tissue-engineered cartilage comprising only cells and cell-produced extracellular matrix is considered valuable as there is no need to consider problems associated with the absorption of scaffold materials and the generation of immune responses. However, it is exceedingly difficult to produce large-sized complex shapes of cartilage without the use of scaffolds. In this study, we describe the production of shape-designable cartilage using a novel cell self-aggregation technique (CAT) and chondroprogenitor cells derived from human induced pluripotent stem cells as the source. The method described does not require special equipment such as bio-3D printers, and the produced tissue can be induced into well-matured cartilage with abundant cartilage matrix in vitro. Using CAT, we were able to generate cartilage in the form of rings or tubes with adjustable inner diameter and curvature, over a range of several centimeters, without the use of scaffolds. The in vitro fabrication of shape-designable cartilage using CAT will undoubtedly contribute to developments in the field of facial plastic surgery.&#xD.

DOI： 10.1088/1748-605X/ad02d1

PubMed

researchmap

ヒトiPS細胞由来肢芽間葉系細胞の発生機序の検討

高尾知佳, 大曽根達則, 山田大祐, 中田英二, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 8 ) S1599 - S1599 2023年8月

ヒトiPS細胞由来肢芽間葉系細胞を用いた骨再建法の開発

佐藤浩平, 高尾知佳, 中田英二, 藤澤佑樹, 山田大祐, 上原健敬, 藤原智洋, 依光正則, 国定俊之, 尾崎敏文, 宝田剛志

日本整形外科学会雑誌 97 ( 8 ) S1868 - S1868 2023年8月

悪性末梢神経鞘腫瘍におけるPRRX1の悪性化因子としての役割

たき平将太, 中田英二, 板野拓人, 片山晴喜, 藤原智洋, 国定俊之, 山田大祐, 高尾知佳, 宝田剛志, 尾崎敏文

日本整形外科学会雑誌 97 ( 8 ) S1890 - S1890 2023年8月

　前のページ - 次のページ　

<寳田 剛志>

論文 - 寳田 剛志

<寳田　剛志>

論文 - 寳田　剛志