普罗格拉努林增强了移植的人类iPS细胞衍生的脑神经元的移植
Keitaro Yamagami1,2, Bumpei Samata1, Daisuke Doi1
1Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Stem cells translational medicine
|September 28, 2024
概括
复合人体前列腺素 (rhPGRN) 增强了用于细胞替代疗法的人类诱导多能干细胞衍生脑器官 (hiPSC-COs) 的存活率和移植. 这种神经营养因子在脑损伤模型中促进神经细胞延伸和移植衍生的神经元集成.
科学领域:
- 神经科学是一个神经科学.
- 再生医学是一种再生医学.
- 干细胞生物学 干细胞生物学
背景情况:
- 使用大脑器官 (COs) 的细胞替代疗法在中风或创伤性脑损伤后的神经回路重建方面显示出前景.
- 成功移植需要有效的移植和神经细胞延伸.
- 受伤后移植延迟1周可能会创造一个更有利的宿主环境.
研究的目的:
- 为了研究创伤后脑损伤0周和1周脑组织之间的基因表达差异.
- 评估复合人性孕原蛋白 (rhPGRN) 对人类诱导的多能干细胞衍生COs (hiPSC-COs) 的神经保护和再生效应.
- 评估rhPGRN对hiPSC-CO移植结果在体内的影响.
主要方法:
- 在受伤后的不同时间点对脑组织进行转录组比较.
- 在氧化应激下对hiPSC-CO神经元存活的体外评估与rhPGRN治疗.
- 在体内移植hiPSC-COs与或没有 rhPGRN预处理,然后进行组织学分析.
主要成果:
- rhPGRN显著增加了氧化应激下分离的hiPSC-CO神经元的存活率,通过通过Akt酸化来降低亡.
- rhPGRN预处理显著提高了hiPSC-CO植入效率,并促进了神经元沿宿主皮质脊柱通道的延长.
- 移植后3个月的组织学分析显示,在接受rhPGRN治疗的接受者中,移植衍生的脑下投影神经元的丰富性更大.
结论:
- 受伤后一周的大脑环境可能比受伤后立即更有利于细胞移植.
- rhPGRN作为一种强大的神经营养因子,增强hiPSC-CO的生存,移植和功能整合.
- rhPGRN具有显著的潜力,可以提高基于hiPSC-CO的细胞疗法在神经修复方面的疗效.
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