成果報告書詳細
管理番号20140000000409
タイトル*平成25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2014/8/20
報告書年度2013 - 2013
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

Author; Osaka University, Nipro Corporation

1. Searching and restructuring of stem cell niche
The ability of polydom as the niche for cardiac stem cells was examined by cultivating cardiac stem cells on polydom under the condition where cardiomyocyte differentiation was induced. Full-length polydom was found most capable of promoting cardiomyocyte differentiation.

2. Development of recruitment and differentiation factor of stem cell
Matrix molecules, such as type I collagen, type IV collagen, laminin and fibronectin, were evaluated for enhancing PDGFRα-positive MSC adhesion to the culture dish.
To elucidate underlying mechanisms of cardio-protective effect of leukemia inhibitory factor (LIF) after myocardial infarction, we examined the effect of LIF on neurite growth of neurons obtained from superior cervical ganglion of neonatal rats.
From the stability tests of ONO-1301MS, an unknown impurity over the reporting threshold in ICH guideline was detected in pharmaceutical products. We also performed the preliminary toxicological experiments by subcutaneous administration to rats and local application by sticking on mini-pig heart at doses given sufficient systemic/local exposure, and found out the toxicological profile of ONO-1301MS. Based on those results we have been conducting a full-scale preclinical toxicity study.

3. Development of self-regenerative cardiovascular device
1)Drug delivery systems for leukemia inhibitory factor (LIF) of a cardiac differentiation factor were developed by using cationized gelatin hydrogels.
When incorporated into cationized gelatin hydrogels, LIF was released from the hydrogel in vivo as a result of the hydrogel degradation. We also investigated the controlled release of HMGB1 A-box peptide with an activity to morbilize bone marrow-derived mesenchymal stem cells and found that introduction of a strong anionic moiety into gelatin hydrogels is necessary for the controlled release of HMGB1 A-box peptide from hydrogels.

2) Development of integrated cardiac support net & drug delivering system.
Gelatin was chosen as drug delivery medium. Two gelatin incorporated systems were developed. Evaluation of histological change by implantation of cardiac supporting net in chronic heart failure canine model (continued)

3) Development of cardiac support net
We have made two types (absorbable or non-absorbable) of cardiac net in order to fit the dog model of heart failure. We succeeded in recovering Ejection Fraction on dog heart failure model by using these two types of cardiac nets as compared with control group. We were successful of making a collagen thread releasing ono1301 slowly.

4. Development for safety and efficacy evaluation
We performed safety examination on the auto-regenerative device in this study under the non-GLP level. We investigated the device in terms of toxicity, foreign reaction, stimulation, biodegradation and inflammation in the device-implanted mice. We extensively performed histopathological approach for the evaluation.
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