研究者詳細 - 王　英正

MISC - 王　英正

分割表示 146 件中 121 - 140 件目／全件表示 >>

心筋幹細胞移植治療における再生心筋の 2D Speckle Tracking echocardiography を用いた局所心筋機能評価

竹原有史, 塘義明, 田畑泰彦, 松原弘明, 王英正

Japanese journal of medical ultrasonics = 超音波医学 35 S352 2008年4月

3 Human cardiac stem cell biotherapy Integrated with bFGF controlled-release : Two randomized, dose-ranging, controlled preclinical trial(Symposium 12 (SY-12) (M) Clinical Experiences of Regenerative Medicine in Cardiovascular Diseases,Special Program,The 72nd Annual Scientific Meeting of the Japanese Circulation Society)

Takehara Naofumi, Tabata Yasuhiko, Tsutsumi Yoshiaki, Matsubara Hiroaki, Oh Hidemasa

Circulation journal : official journal of the Japanese Circulation Society 72 48 - 48 2008年3月

OE-237 Dose-dependent Functional Recovery of Human Cardiac Stem Cell Transplantation Combined with Control-Delivery of Angiogenic Growth Factor in Chronic Myocardial Infarction(Regeneration(angiogenesis/myocardial regeneration)(01)(M),Oral Presentation(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)

Takehara Naofumi, Tsutsumi Yoshiaki, Tateishi Kento, Ogata Takehiro, Ueyama Tomomi, Takahashi Tomosaburo, Tanaka Hideo, komeda Masashi, Yamagishi Masaaki, Yaku Hitoshi, Tabata Yasuhiko, Matsubara Hiroaki, Oh Hidemasa

Circulation journal : official journal of the Japanese Circulation Society 72 240 - 240 2008年3月

Regeneration therapy for cardiac repair by autologous human heart-derived stem cells from biopsy samples

Hiroaki Matsubara, Kento Tateishi, Hidemasa Oh

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 44 ( 2 ) 435 - 435 2008年2月

Secreted phosphoprotein 1 enhances proliferative self-renewal through PI3K/Akt signaling in skeletal myosphere-derived progenitor cells

Takehiro Ogata, Tomomi Ueyama, Tetsuya Nomura, Satoshi Asada, Masashi Tagawa, Tomoyuki Makamura, Tomosaburo Takahashi, Hiroaki Matsubara, Hidemasa Oh

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 44 ( 2 ) 448 - 449 2008年2月

Skeletal muscle-derived progenitors capable of differentiating into cardiomyocytes proliferate through myostatin-independent TGF-beta family signaling

Tetsuya Nomura, Tomomi Ueyama, Eishi Ashihara, Kento Tateishi, Satoshi Asada, Norio Nakajima, Koji Isodono, Tomosaburo Takahashi, Hiroaki Matsubara, Hidemasa Oh

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 365 ( 4 ) 863 - 869 2008年1月

記述言語：英語出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

The existence of skeletal muscle-derived stem cells (MDSCs) has been suggested in mammals; however, the signaling pathways controlling MDSC proliferation remain largely unknown. Here we report the isolation of myosphere-derived progenitor cells (MDPCs) that can give rise to beating cardiomyocytes from adult skeletal muscle. We identified that follistatin, an antagonist of TGF-beta family members, was predominantly expressed in MDPCs, whereas myostatin was mainly expressed in myogenic cells and mature skeletal muscle. Although follistatin enhanced the replicative growth of MDPCs through Smad2/3 inactivation and cell cycle progression, disruption of myostatin did not increase the MDPC proliferation. By contrast, inhibition of activin A (ActA) or growth differentiation factor 11 (GDF11) signaling dramatically increased MDPC proliferation via down-regulation of p21 and increases in the levels of cdk2/4 and cyclin D1. Thus, follistatin may be an effective progenitor-enhancing agent neutralizing ActA and GDF11 signaling to regulate the growth of MDPCs in skeletal muscle. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2007.11.087

Web of Science

researchmap

心臓組織内幹細胞を用いた心不全への心筋再生医療の現状

王英正

心電図 2008年

心臓内幹細胞の特性と自己複製制御機構

王英正, 立石健人, 松原弘明

実験医学増刊号 2008年

心不全への再生医療

足立淳郎, 井本裕子, 山口真一郎, 竹原有史, 王英正, 松原弘明

心不全診療マニュアル 2008年

生体組織工学的手法を用いた心筋幹細胞とその特異的増幅因子を導入するハイブリッド移植療法の開発

王英正, 小形岳寛, 野村哲矢, 浅田聡, 上山知己

医科学応用研究財団研究報告 25 173 - 177 2008年

記述言語：日本語出版者・発行元：(公財)鈴木謙三記念医科学応用研究財団

心筋幹細胞Myosphere-derived progenitor cells(MDPCs)をSAGE法を用いて遺伝子発現の解析を行い、SST法を用いてMDPCsより分泌される蛋白の同定を行った。その結果、osteopontin(OPN)が未分化MDPCsの増殖に最も重要である因子である可能性が考えられた。同定したOPNの発現を骨格筋組織由来の細胞およびMDPCsを用いて染色し、その発現量は幹細胞に富むMDPCsにおいて有意に亢進していることが明らかとなった。また、OPN刺激によりMDPCsの細胞数も増加していた。このことから、OPNのMDPCsの増殖にに対する作用が明らかとなった。さらに、OPNの増殖に及ぼす細胞内情報伝達経路の検討を行ったところ、OPN刺激によりAkt/GSK3βが活性化させることが明らかとなった。以上の結果から、phosphoinositide 3-kinaseを介したAkt活性化がOPNによるMDPCsの増殖に重要であると推測された。

J-GLOBAL

researchmap

Therapeutic potential of stem/progenitor cells in human skeletal muscle for cardiovascular regeneration

Tetsuya Nomura, Eishi Ashihara, Kento Tateishi, Tomomi Ueyama, Tomosaburo Takahashi, Masaaki Yamagishi, Toshikazu Kubo, Hitoshi Yaku, Hiroaki Matsubara, Hidemasa Oh

Current Stem Cell Research and Therapy 2 ( 4 ) 293 - 300 2007年12月

記述言語：英語掲載種別：書評論文，書評，文献紹介等

Although myoblast transplantation in patients with ischemic heart failure results in a significant improvement of cardiac function, subsequent studies have consistently shown the myotubes formation in the absence of electromechanical coupling with the neighboring host myocardium, accompanied with the short-term release of paracrine effectors from implanted cells. One major pitfall of using myoblasts is that transplanted cells do not differentiate into cardiomyocytes, which may cause the inherent proarrhythmogenic events. Therefore, whether a discrete subpopulation in heterogeneous muscle-cell cultures is responsible for substantial cardiovascular regeneration has yet to be investigated. We describe here the isolation of progenitor cells from human skeletal muscle. These cells proliferated as non-adherent myospheres in suspension and displayed early embryonic factors and mesenchymal cell-like characteristics. Flow cytometric analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell adhesion molecule abundantly present in myoblasts, was absent in myospheres but was expressed in an adherent cell population containing myogenic precursors. Myosphere-derived progenitor cells (MDPCs) differentiated in culture to produce cardiac, smooth muscle, and endothelial cells. Transplantation of MDPCs into ischemic hearts in NOD/scid mice promoted angiogenesis with substantial cardiovascular regeneration. Our results provide a foundation to further study the cell and biological function of human MDPCs which may have potential therapeutic implications. © 2007 Bentham Science Publishers Ltd.

DOI： 10.2174/157488807782793808

Scopus

PubMed

researchmap

Stage-specific role of endogenous Smad2 activation in cardiomyogenesis of embryonic stem cells

Ryoji Kitamura, Tomosaburo Takahashi, Norio Nakajima, Koji Isodono, Satoshi Asada, Hikaru Ueno, Tomomi Ueyama, Toshikazu Yoshikawa, Hiroaki Matsubara, Hidemasa Oh

CIRCULATION RESEARCH 101 ( 1 ) 78 - 87 2007年7月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

The role of Smads and their specific ligands during cardiomyogenesis in ES cells was examined. Smad2 was activated bimodally in the early and late phases of cardiac differentiation, whereas Smad1 was activated after the middle phase. Nodal and Cripto were expressed in the early stage and then downregulated, whereas transforming growth factor-beta and activin were expressed only in the late phase. Suppression of early Smad2 activation by SB- 431542 produced complete inhibition of endodermal and mesodermal induction but augmented neuroectodermal differentiation, followed by poor cardiomyogenesis, whereas inhibition during the late phase alone promoted cardiomyogenesis. Inhibitory effect of Smad2 on cardiomyogenesis in the late phase was mainly mediated by transforming growth factor-beta, and inhibition of transforming growth factor-beta- mediated Smad2 activation resulted in a greater replicative potential in differentiated cardiac myocytes and enhanced differentiation of nonmyocytes into cardiac myocytes. Thus, endogenous Smad2 activation is indispensable for endodermal and mesodermal induction in the early phase. In the late phase, endogenous transforming growth factor-beta negatively regulates cardiomyogenesis through Smad2 activation by modulating proliferation and differentiation of cardiac myocytes.

DOI： 10.1161/CIRCRESAHA.106.147264

Web of Science

researchmap

Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway

Takehiro Ogata, Tomomi Ueyama, Tetsuya Nomura, Satoshi Asada, Masashi Tagawa, Tomoyuki Nakamura, Tomosaburo Takahashi, Hiroaki Matsubara, Hidemasa Oh

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 359 ( 2 ) 341 - 347 2007年7月

記述言語：英語出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

We have reported that skeletal myosphere-derived progenitor cells (MDPCs) can differentiate into vascular cells, and that MDPC transplantation into cardiomyopathic hearts improves cardiac function. However, the autocrine/paracrine molecules and underlying mechanisms responsible for MDPC growth have not yet been determined. To explore the molecules enhancing the proliferation of MDPCs, we performed serial analysis of gene expression and signal sequence trap methods using RNA isolated from MDPCs. We identified osteopontin (OPN), a secretory molecule, as one of most abundant molecules expressed in MDPCs. OPN provided a proliferative effect for MDPCs. MDPCs treated with OPN showed Akt activation, and inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway repressed the proliferative effect of OPN. Furthermore, OPN-pretreated MDPCs maintained their differentiation potential into endothelial and vascular smooth muscle cells. These findings indicate an important role of OPN as an autocrine/paracrine molecule in regulating the proliferative growth of muscle-derived angiogenic progenitor cells via the PI3K/Akt pathway. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2007.05.104

Web of Science

researchmap

心臓幹細胞移植による心筋再生医療の臨床応用への可能性 (特集心筋再生と心筋保護)

王英正

呼吸と循環 55 ( 7 ) 721 - 726 2007年7月

Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration

Kento Tateishi, Eishi Ashihara, Naofumi Takehara, Tetsuya Nomura, Shoken Honsho, Takuo Nakagami, Shigehiro Morikawa, Tomosaburo Takahashi, Tomomi Ueyama, Hiroaki Matsubara, Hidemasa Oh

JOURNAL OF CELL SCIENCE 120 ( 10 ) 1791 - 1800 2007年5月

記述言語：英語出版者・発行元：COMPANY OF BIOLOGISTS LTD

Recent studies have shown that cardiac stem cells (CSCs) from the adult mammalian heart can give rise to functional cardiomyocytes; however, the definite surface markers to identify a definitive single entity of CSCs and the molecular mechanisms regulating their growth are so far unknown. Here, we demonstrate a single-cell deposition analysis to isolate individually selected CSCs from adult murine hearts and investigate the signals required for their proliferation and survival. Clonally proliferated CSCs express stem cell antigen-1 (Sca-1) with embryonic stem (ES) cell-like and mesenchymal cell-like characteristics and are associated with telomerase reverse transcriptase (TERT). Using a transgene that expresses a GFP reporter under the control of the TERT promoter, we demonstrated that TERTGFP-positive fractions from the heart were enriched for cells expressing Sca-1. Knockdown of Sca-1 transcripts in CSCs led to retarded ex vivo expansion and apoptosis through Akt inactivation. We also show that ongoing CSC proliferation and survival after direct cellgrafting into ischemic myocardium require Sca-1 to upregulate the secreted paracrine effectors that augment neoangiogenesis and limit cardiac apoptosis. Thus, Sca-1 might be an essential component to promote CSC proliferation and survival to directly facilitate early engraftment, and might indirectly exert the effects on late cardiovascular differentiation after CSC transplantation.

DOI： 10.1242/jcs.006122

Web of Science

researchmap

Skeletal myosphere-derived progenitor cell transplantation promotes neovascularization in delta-sarcoglycan knockdown cardiomyopathy

Tetsuya Nomura, Eishi Ashihara, Kento Tateishi, Satoshi Asada, Tomomi Ueyama, Tomosaburo Takahashi, Hiroaki Matsubara, Hidemasa Oh

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 352 ( 3 ) 668 - 674 2007年1月

記述言語：英語出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

Bone marrow cells have been shown to contribute to neovascularization in ischemic hearts, whereas their impaired maturation to restore the delta-sarcoglycan (delta-SG) expression responsible for focal myocardial degeneration limits their utility to treat the pathogenesis of cardiomyopathy. Here, we report the isolation of multipotent progenitor cells from adult skeletal muscle, based on their ability to generate floating-myospheres. Myosphere-derived progenitor cells (MDPCs) are distinguishable from myogenic C2C12 cells and differentiate into vascular smooth muscle cells and mesenchymal progeny. The mutation in the delta-SG has been shown to develop vascular spasm to affect sarcolemma structure causing cardiomyopathy. We originally generated delta-SD knockdown (KD) mice and transplanted MDPCs into the hearts. MDPCs enhanced neoangiogenesis and restored delta-SG expression in impaired vasculatures through trans-differentiation, leading to improvement of cardiac function associated with paracrine effectors secretion. We propose that MDPCs may be the promising progenitor cells in skeletal muscle to treat delta-sarcoglycan complex mutant cardiomyopathy. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2006.11.097

Web of Science

researchmap

Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3 beta signaling

Kento Tateishi, Eishi Ashihara, Shoken Honsho, Naofumi Takehara, Tetsuya Nomura, Tomosaburo Takahashi, Tomomi Ueyama, Masaaki Yamagishi, Hitoshi Yaku, Hiroaki Matsubara, Hidemasa Oh

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 352 ( 3 ) 635 - 641 2007年1月

記述言語：英語出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardio-myocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3 beta may be crucial modulators for hCSC maintenance in human heart. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2006.11.096

Web of Science

researchmap

ヒト心筋組織幹細胞研究の現状

王英正

分子血管病 2007年

心筋細胞の再生医療

王英正

メディカルビューポイント 2007年

Isl-1前駆細胞

王英正

Annual Review 循環器 2007年

　前のページ - 次のページ　

<王 英正>

MISC - 王 英正

<王　英正>

MISC - 王　英正