The role of Thymosin beta4 in adult bone marrow stem cell transplantation for cardiac repair

胸腺肽β4在成人骨髓干细胞移植心脏修复中的作用

• 批准号: G0802269/1
• 负责人: Chia Yeo
• 金额: $ 32.83万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802269%2F1
• 关键词: role; Thymosin; beta4; adult; bone

3 out of 10 heart attack survivors will encounter untoward complications from the damaged heart within 1 year. Evidence suggests that delivering bone marrow stem cells (BMSCs) to the injured heart can aid repair, possibly through the release of protective proteins. Recent work has demonstrated that a protein, Thymosin beta4 (Tß4), stimulates cells in the outer region of the adult mouse heart to make new blood vessels. Tß4 is produced by BMSCs at high levels and when artificially made Tß4 was injected into mice after a heart attack, a smaller area of heart damage and better heart function resulted. Therefore, we wish to explore if the beneficial effect of BMSCs delivered to injured hearts is mediated by Tß4. We will isolate BMSCs from adult mice and heart attack patients and assess factors controlling Tß4 release in heart attack conditions. By switching on and off BMSC Tß4 production, the effect of Tß4 on the heart will be examined in experimental models using different cultured heart cells and genetically altered mice. Lastly, to understand the body‘s natural Tß4 response to heart injury, blood Tß4 levels will be measured in patients receiving immediate standard care for heart attack and after BMSC transplantation.

10名心脏病发作幸存者中有3人会在1年内遇到心脏受损的不良并发症。有证据表明，将骨髓干细胞（BMSC）输送到受伤的心脏可以帮助修复，可能是通过释放保护蛋白。最近的研究表明，一种蛋白质，胸腺素β 4（T β 4），刺激成年小鼠心脏外部区域的细胞产生新的血管。BMSC以高水平产生T β 4，当人工制造的T β 4在心脏病发作后注射到小鼠体内时，心脏损伤面积较小，心脏功能更好。因此，我们希望探索BMSC递送到受损心脏的有益作用是否由T β 4介导。我们将从成年小鼠和心脏病发作患者中分离BMSC，并评估心脏病发作条件下控制T β 4释放的因素。通过开启和关闭BMSC T β 4的产生，T β 4对心脏的影响将在使用不同培养的心脏细胞和遗传改变的小鼠的实验模型中进行检查。最后，为了了解身体对心脏损伤的天然T β 4反应，将在接受心脏病发作的立即标准护理和BMSC移植后的患者中测量血液T β 4水平。