Injectable Nano-Scaffolds, Hydroxyapatite-Polymer Nanocomposite Microsphere, Enhance the Therapeutic Angiogenesis by Cell Transplantation

可注射纳米支架、羟基磷灰石-聚合物纳米复合微球，通过细胞移植增强治疗性血管生成

• 批准号: 20592102
• 负责人: FUKUMOTO Shinya
• 金额: $ 3.08万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20592102/
• 关键词: 創傷治癒学; 虚血性難治性潰瘍; 血管新生療法

Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis against patients with a variety of ischemic disease; however, the clinical success to date has been still limited. We have reported that nano-scaled sintered hydroxyapatite (HAp)-coating on artificial grafts reveals marked cell-adhesiveness, safety and high tissue-affinity. With this nanotechnology, the inorganic, biodegradable and injectable scaffold, HAp-coated poly L-lactic acid (PLLA) microsphere, has been generated : named nano-scaffold (NS). In this study, we examined its usefulness in cell-based therapeutic angiogenesis. Bone marrow-mononuclear cells (BMC) alone, with uncoated PLLAs (LA), or with HAp-coated microspheres (nano-scaffold : NS), were intramuscularly injected into mice ischemic hind-limbs generated by femoral artery occlusion. Kaplan-Meier analysis demonstrated that NS+BMC treatment markedly prevented limb necrosis after the operation (vs. BMC alone, and LA+BMC). Roles of NS to sustain BMC in ischemic tissues were demonstrated by the findings that immunohistochemistry revealed NS and BMC co-localized, and that NS+BMC group exhibited significantly elevated intramuscular levels of proangiogenic cytokines in ischemic tissues as compared with BMC alone. We demonstrated usefulness of injectable scaffold as an enhancer for cell-based therapeutic angiogenesis.

临床试验证明了基于细胞的治疗性血管生成对患有各种缺血性疾病的患者的有效性;然而，迄今为止的临床成功仍然有限。我们已经报道了在人工移植物上的纳米级烧结羟基磷灰石（HAp）涂层显示出显著的细胞增殖性、安全性和高组织亲和力。利用这种纳米技术，制备了无机的、可生物降解的、可注射的支架--羟基磷灰石包覆的聚L-乳酸（PLLA）微球，称为纳米支架（NS）。在这项研究中，我们研究了其在基于细胞的治疗性血管生成中的有用性。将骨髓单个核细胞（BMC）单独、与未涂覆的PLLA（LA）或与HAp涂覆的微球（纳米支架：NS）肌肉内注射到由股动脉闭塞产生的小鼠缺血后肢中。Kaplan-Meier分析表明，NS+BMC治疗明显防止了术后肢体坏死（与单独BMC和LA+BMC相比）。NS和BMC共定位于缺血组织中，并且NS+BMC组与单独BMC组相比，缺血组织中的促血管生成细胞因子的肌内水平显著升高，证实了NS维持缺血组织中BMC的作用。我们证明了可注射支架作为基于细胞的治疗性血管生成的增强剂的有用性。

项目成果

末梢血管疾患の内科的診療と最近の取り組み

周围血管疾病的内科治疗及近期进展

• 发表时间: 2010
• 作者: 松崎恭一;他;福本真也
• 通讯作者: 福本真也

新しい細胞移植療法のためのナノアパタイトコーティング微粒子材料の開発

开发用于新型细胞移植疗法的纳米磷灰石涂层颗粒材料

• 发表时间: 2010
• 期刊: バイオマテリアル生体材料 28
• 作者: 岡田正弘;福本真也;三間洋平;藤井秀司;古薗勉
• 通讯作者: 古薗勉

医療用組成物および医療用キット

医疗组合物和医疗包

• 发表时间: 2009

Regions of arterial stenosis and clinical factors determining transcutaneous oxygen tension in patients with peripheral arterial disease

外周动脉疾病患者动脉狭窄部位及决定经皮氧分压的临床因素

• 发表时间: 2010
• 期刊: J Atheroscler Thromb 17
• 作者: Ueno H;総12名;Inaba M (11番目)
• 通讯作者: Inaba M (11番目)

Injectable Cell Scaffolds, Hydroxyapatite. Polymer Nanocomposite Microsphere, Enhance the Therapeutic Angiogenesis by Cell Transplantation.

可注射细胞支架，羟基磷灰石。

• 发表时间: 2010
• 作者: Yohei Mima;Shinya Fukumoto;Hidenori Koyama;Masahiro Okada;Shinji Tanaka;Masahiro Murayama;Yohiko Otsuka;Tsutomu Furuzono;Masaaki Inaba;Yoshiki Nishizawa
• 通讯作者: Yoshiki Nishizawa