Role of T cells during stem cell-driven regeneration: towards design of efficient stem cell-based therapies

T 细胞在干细胞驱动的再生过程中的作用：设计有效的基于干细胞的疗法

基本信息

批准号：
15H06348
负责人：
MARTINO Mikael
金额：
$ 1.91万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2015
资助国家：
日本
起止时间：
2015-08-28 至 2017-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15H06348/
关键词：
再生医療免疫学幹細胞 T細胞バイオマテリアル

项目摘要

As we are facing an aging population, regenerative medicine will play a key role in patient care. While the field is becoming one of the next major innovations in healthcare, clinical translations of therapies are often very modest. For this research project, I hypothesized that tissue regeneration is strongly regulated by a crosstalk between the adaptive immune system and tissue-resident stem cells. Specifically, subsets of T cells could act as either “antiregenerative” or as “proregenerative”, by regulating stem cell functions.One the main goal for FY2015 was to determine which types of T cells and when are they recruited during stem cell-driven tissue healing. Using a bone regeneration model in the mouse, I found that T cells are recruited about 10 days following bone injury. The number of T cell is higher when the defects are treated with mesenchymal stem cells, especially the number of regulatory T cells.The second goal was to determine whether T cells modulate stem cell-driven tissue healing. I found that mice with more regulatory T cells (regulatory T cells injected i.v.) significantly regenerate bone faster. In addition, when defect are treated with mesenchymal stem cells, mice with more regulatory T cells significantly regenerate bone faster.The results of this research will serve as a base to design novel stem cell-based therapies.

当我们面临老龄化的人口时，再生医学将在患者护理中起关键作用。尽管该领域正在成为医疗保健领域的下一个主要创新之一，但疗法的临床翻译通常非常适中。对于该研究项目，我假设组织再生受到自适应免疫系统和组织居住的干细胞之间的串扰。具体而言，通过控制干细胞功能，T细胞的亚群可以用作“抗晶剂”或“促生生物”。2015财年的主要目标是确定哪种类型的T细胞，何时在干细胞驱动的组织组织愈合过程中募集。使用小鼠中的骨再生模型，我发现在骨损伤后约10天募集了T细胞。当缺陷用间充质干细胞（尤其是调节T细胞的数量）处理时，T细胞的数量较高。第二个目标是确定T细胞是否调节干细胞驱动的组织愈合。我发现具有更多调节性T细胞（调节性T细胞注入静脉注射的小鼠）的小鼠会更快地再生骨。此外，当用间充质干细胞处理缺陷时，具有更具调节性T细胞的小鼠会更快地再生骨。这项研究的结果将成为设计新型干细胞疗法的基础。