Derivation of acquired tolerance by a fetal period stem cell transplantation : A fundamental research for neonatal xenogenic heart transplantation.

胎儿期干细胞移植获得性耐受的推导：新生儿异种心脏移植的基础研究。

• 批准号: 14571573
• 负责人: YOSHINAGA Mitsuhiro
• 金额: $ 1.73万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571573/
• 关键词: regenerative medicine; stem cell transplantation; Inflammation; 臓器再生; 移植; 炎症反応; 幹細胞

ObjectiveInflammation is a natural defense mechanism for an invasion from foreign bodies, but excessive reaction occasionally injures the tissues or the organ. On the other hand, inflammatory reaction is an initial reaction of organ regeneration.Since the regeneration process, including the resultant reactions, does not take effect enough in humans, there is a possibility that inflammation does not lead to organic ecphoria.This study analyzes the injury and regeneration reactions that occur in relation to inflammation and how the latter relieves tissue damage to regulate the balance for regeneration to occur.Our purpose is to enable efficient organ regeneration by introducing exogenous stem cell alongside the endogenous regenerative ability of humans.Methods and resultsIn this study, organic regeneration wherein condition of tissue architecture is not important was tried. It was considered that the distance to clinical application was comparatively short.We tried to establish the artif … More icial differentiation of pancreatic islet cells concretely.For the purpose of investigating what condition is better for inducing differentiation to β cell, C57/BL6 mice and ApoEKO mice at eight-week of age were assumed recipient and bone marrow transplantation was performed as donor in GFP laboratory mice. Radiation exposure at fatal dose was performed before bone marrow transplantation for each recipient. The pancreas of recipient mice was delivered after breeding more than one year and frozen section was made.For observation of pancreatic islet cells, insulin and glucagon were dyed with fluorescent immunostaining.The bone marrow cell of GFP mice was introduced into the pancreas of the recipient mice.More remarkable cellular differentiation was seen in ApoE knockout mice as compared to C57/BL6 mice. Furthermore, insulin and glucagon, which were stained by immunofluorescence, were seen in GFP mice.As for the GFP donor bone marrow cell, it was suggested that induction to pancreatic β/α cell by ApoE knockout mouse with a good inflammatory reaction was effective. Less

目的炎症是异物侵入的自然防御机制，但过度反应有时也会损伤组织或器官。另一方面，炎症反应是器官再生的初始反应。由于再生过程，包括由此产生的反应，在人体中没有充分发挥作用，因此炎症有可能不会导致器质性快感。本研究分析与炎症相关的损伤和再生反应，以及炎症如何缓解组织损伤，调节再生平衡。我们的目的是使器官能够高效地再生。 通过引入外源干细胞以及人类内源再生能力来实现再生。方法和结果在本研究中，尝试了组织结构条件不重要的有机再生。认为离临床应用的距离比较短。我们试图具体建立胰岛细胞的人工分化。为了研究什么条件更适合诱导分化为β细胞，以8周龄的C57/BL6小鼠和ApoEKO小鼠为受体，并在GFP实验小鼠中进行骨髓移植作为供体。在对每个接受者进行骨髓移植之前进行致命剂量的辐射暴露。饲养一年多后，将受体小鼠的胰腺交付并制作冰冻切片。为了观察胰岛细胞，用荧光免疫染色对胰岛素和胰高血糖素进行染色。将GFP小鼠的骨髓细胞引入受体小鼠的胰腺中。与C57/BL6小鼠相比，ApoE敲除小鼠中看到更显着的细胞分化。此外，在GFP小鼠中还观察到免疫荧光染色的胰岛素和胰高血糖素。对于GFP供体骨髓细胞，表明炎症反应良好的ApoE敲除小鼠诱导胰腺β/α细胞是有效的。较少的