成果報告書詳細
管理番号20130000001039
タイトル*平成24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2013/11/20
報告書年度2012 - 2012
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
英文要約Title; Research and Development of Next-generation Regenerative Technology / Basic research and development of cell-free devices for regenerative medicine

1. Searching and restructuring of stem cell niche
A novel extracellular matrix protein, polydom has been identified in the epicardium. The cardiac stem cells adhered to the polydom-coated substrates and proliferated to form colonies, indicating that polydom functions as the niche for cardiac stem cells. Ten laminin isoforms as well as polydom have been successfully endowed with the capability of binding to collagens.
2. Development of recruitment and differentiation factor of stem cell
Research progress concerning HMGB1-induced tissue regeneration is as follows;
1) HMGB1 induces expression of leukemia inhibitory factor (LIF) in bone marrow-derived mesenchymal stem cells.
2) Specific cell surface markers of circulating bone marrow-derived mesenchymal stem cells are PDGFRa+CXCR4+/CD45-TER119-.
3) Specific domain for mobilizing mesenchymal stem cells from bone marrow to get into injured tissue is locating within N-terminal 44 amino acid residues of HMGB1 A-box.
Using a genetic fate-mapping mouse model, we showed that LIF proliferates cardiac side population (SP) cells and enhances myocardial regeneration in part by activating SP cells after myocardial infarction.
3.Development of self-regenerative cardiovascular device
Drug delivery systems for ONO-1301 of a water-insoluble drug were developed by using hydrogels consisting of gelatin and L-lactic acid oligomer. The cardiac mesh devise enabling ONO-1301 to release in a controlled manner was designed as a devise to induce the recruitment of stem cells by ONO-1301 released from the devise. Controlled release of ONO-1301 from the devise was investigated. We have made a type of biodegradable cardiac net in order to fit the dog model of heart failure. We have made two pieces of gelatin film to get slow-release drug-delivery type. We succeeded to recover Ejection Fraction on dog heart failure model as compared with control group.
Development of cardiac support net by computer regulated knitting machine is as follows; (Shimaseiki Co.)
1) Evaluation of the strain-stress relationship of cardiac support net knitted by the various threads (regular braided polyester threads, ultra-fine polyester threads, polyester/polybuthyltelefutarate combination threads) 2) Evaluation of the gelatin immersion to cardiac supporting net on strain-stress relationship.
4. Development for safety and efficacy evaluation
We performed histo-pathological analysis for toxicological approach toward the heart treated with the “Save Heart” device in the animal model. ONO-1301 up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model. We examined evaluation of histological change by implantation of cardiac supporting net to canine DCM model.
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