Construction of Tissue-Engineered Vascular Autograft using Bone Marrow Derived Stem Cells and Biodegradable Scaffold and It's Clinical Application

骨髓干细胞和生物可降解支架构建组织工程自体血管及其临床应用

• 批准号: 16591415
• 负责人: MATSUMURA Goki
• 金额: $ 2.24万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591415/
• 关键词: Regenerative Medicine; Tissue Engineering; Bone Marrow; Biodegradable Scaffold; Tissue-Engineered vessel; Mononuclear Bone Marrow; Endothelial Cells; Mechanical Properties; 生体吸収素材

This study demonstrates the evaluation of the endothelial function and mechanical properties of tissue-engineered vascular autografts (TEVAs) constructed with autologous mononuclear-bone marrow cells (MN-BMCs) and a biodegradable scaffold using a canine inferior vena cava (IVC) model.MN-BMCs were obtained from a dog and seeded onto a biodegradable tubular scaffold consisting of polyglycolide fiber and poly(1-lactide-co-ε-caprolactone) sponge. This scaffold was implanted in the IVC of the same dog on the day of surgery. TEVAs were analyzed biochemically, biomechanically and histologically after implantation. When TEVAs were explanted and stimulated with acetylcholine at 1 month, they dose dependently produced nitrates and nitrites. N^G-nitro-L-arginine methylester significantly inhibited these reactions. On the stimulation by acetylcholine, factor VIII-positive cells of TEVAs produced eNOS proteins, and the ratio of eNOS/s17 mRNA were similar among native IVC, 1-and 3-months TEVAs. TEVAs had similar biochemical properties and wall thickness as native IVC at 6 months after implantation, and tolerated venous pressure well without any problems such as calcification.These results indicate that TEVAs are biocompatible material with functional endothelial cells and biomechanical properties without unwanted side-effects.

本研究展示了使用犬下腔静脉 (IVC) 模型评估由自体单核骨髓细胞 (MN-BMC) 和可生物降解支架构建的组织工程自体血管移植物 (TEVA) 的内皮功能和机械性能。MN-BMC 从狗身上获得，并接种到可生物降解的管状支架上 由聚乙交酯纤维和聚(1-丙交酯-co-ε-己内酯)海绵组成。该支架在手术当天被植入同一只狗的下腔静脉中。植入后对 TEVA 进行生化、生物力学和组织学分析。当 TEVA 被外植并在 1 个月时用乙酰胆碱刺激时，它们会剂量依赖性地产生硝酸盐和亚硝酸盐。 N^G-硝基-L-精氨酸甲酯显着抑制这些反应。在乙酰胆碱刺激下，TEVA 的因子 VIII 阳性细胞产生 eNOS 蛋白，并且 eNOS/s17 mRNA 的比率在天然 IVC、1 个月和 3 个月的 TEVA 中相似。植入后 6 个月，TEVA 具有与天然 IVC 相似的生化特性和壁厚度，并且能够很好地耐受静脉压力，没有任何钙化等问题。这些结果表明，TEVA 是具有功能性内皮细胞和生物力学特性的生物相容性材料，没有不良副作用。

项目成果

Mid-term clinical results of tissue engineered vascular autografts seeded with autologous bome marrow cells

自体骨髓细胞接种组织工程自体血管移植物的中期临床结果

• 发表时间: 2005
• 期刊: J Thorac Cardiovasc Surg 129
• 作者: Shin'oka T;Matsumura G;Hibino N;Naito Y;Watanabe M;Konuma T;Sakamoto T;Nagatsu M;Kurosawa
• 通讯作者: Kurosawa

臨床応用が実現した再生医療

再生医学及其临床应用

• 发表时间: 2005
• 期刊: 薬の知識 56
• 作者: 宮川 和也;成田 年;富田 真理子;宮竹 真由美;鈴木 勉;高井 治;新岡俊治
• 通讯作者: 新岡俊治

Clinical results of tissue-engineered vascular autografts seeded with autologous bone marrow cells

自体骨髓细胞接种的组织工程自体血管移植物的临床结果

• 发表时间: 2004
• 期刊: Nippon Geka Gakkai Zasshi 105,8
• 作者: Shin'Oka;T
• 通讯作者: T

Autopericardial patch tracheoplasty for tracheal stenosis after arterial switch operation

自体心包补片气管成形术治疗动脉调转术后气管狭窄

• 发表时间: 2005
• 期刊: J Card Surg 20
• 作者: Takiguchi M;Aoki M;Shin'oka T;Hiramatsu T;Imai Y
• 通讯作者: Imai Y

The tissue-engineered vascular graft using bone marrow without culture

• DOI: 10.1016/j.jtcvs.2004.10.030
• 发表时间: 2005-05-01
• 期刊: JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
• 影响因子: 6
• 作者: Hibino, N;Shin'oka, T;Kurosawa, H
• 通讯作者: Kurosawa, H