成果報告書詳細
管理番号20120000000797
タイトル*平成23年度中間年報 「次世代機能代替技術の研究開発/次世代再生医療技術の研究開発/生体内で自己組織の再生を促すセルフリー型再生デバイスの開発(幹細胞ニッチ制御による自己組織再生型心血管デバイスの基盤開発)」
公開日2012/9/11
報告書年度2011 - 2011
委託先名国立大学法人大阪大学 ニプロ株式会社
プロジェクト番号P10004
部署名バイオテクノロジー・医療技術部
和文要約和文要約等以下本編抜粋:1. 研究開発の内容及び成果等
1 幹細胞ニッチの探索と再構築技術の開発
(担当:国立大学法人 大阪大学 蛋白質研究所)
1?1 幹細胞ニッチを構築する基底膜分子の同定とその機能評価
GFP保持細胞として心臓幹細胞を可視化する技術を開発し、この細胞が主に心外膜に局在することを明らかにした。また、GFP保持細胞の近傍に発現する基底膜分子を網羅的に検索し、コラーゲンXVIIIなど、複数の幹細胞ニッチ分子の候補蛋白質を同定した。
英文要約Title; Research and Development of Next-generation Regenerative Technology / Basic research and development of cell-free devices for regenerative medicine
Author; Osaka University, Nipro Corporation
1. Searching and restructuring of stem cell niche
A novel imaging protocol for identification of cardiac stem cells was developed by utilizing pulse labeling of cells with GFP. Several candidates that comprise the cardiac stem cell niche were identified. A novel technology that endows collagen fibrils with the cell-adhesive activity of laminins was developed.
2. Development of recruitment and differentiation factor of stem cell
We revealed that mesenchymal stem cells (MSCs) which egress from bone marrow by HMGB1 were recruited to the injured tissue by SDF-1/CXCR4 axis. When gelatin-hydrogel containing SDF-1 was transplanted subcutaneously in mice, PDGFR-α (+) MSCs were significantly accumulated in the gel.
 Screening of various growth factors and cytokines for their cardiogenic activity using adipose tissue-derived stem cells resulted in the identification of leukemia inhibitory factor (LIF) as a potent cardiogenic growth factor. We also found that LIF promotes stem cell-derived cardiomyogenesis after myocardial infarction using in vivo fate mapping technique.
3.Development of self-regenerative cardiovascular device
In this year, the molecular design of hydrogels for the controlled release of water-insoluble drugs is mainly focused by combining gelatin and L-lactic acid oligomer of a clinically applicable biodegradable polymer. Briefly, gelatin hydrogels incorporating statin-micelles were prepared through chemical crosslinking of mixed solution of gelatin and statin-micelles. When evaluating both the in vitro simvastatin release and the in vitro degradation for the gelatin hydrogels incorporating statin-micelles, we found that simvastatin was released from the hydrogels as a result of the hydrogel degradation.
We have examined the extraction of main technologies and the basic design to develop the devices like cell niche in vivo which have function to control the stem cell proliferation and differentiation in addition to it to enhance the biological activation by the released inducing factors and the differentiation promoting factors. We have constructed the basal structure of mesh device made of biodegradable material and confirmed that we could coat the device with released factors.
4.Development for safety and efficacy evaluation
We perform standardization of cells by detection of N-Acetylneuraminic acid and genomic alterations by comparative genomic hybridization (CGH) to validate safety index of regenerative tissue.
From in vivo pharmaco-dynamic experiments with ONO-1301 microsphere applied on heart as gel-form it was demonstrated that concentrations of ONO-1301 observed at ventricles were remarkably higher for 2 weeks than those observed in plasma. These finding suggested ONO-1301 microsphere would be good option for getting local action at heart.
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