异位囊泡调节内皮代谢,通过PD1/PDL1轴改善缺血性视网膜病变
Yutong Jing1,2, Wanmin Zhao2, Ziyi Zhou1
1Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Advanced healthcare materials
|February 27, 2024
概括
来自干细胞的瘤囊泡 (apoVs) 显示出治疗缺血视网膜病变的前景. 这些SHED-apoVs通过PD1/PDL1轴调节内皮细胞糖解,减少病变性血管生成并改善血管重塑.
科学领域:
- 眼科医生 眼科 眼科
- 再生医学是一种再生医学.
- 细胞生物学 细胞生物学
背景情况:
- 病理性血管新生和微血管改造在缺血性视网膜疾病中导致失明.
- 目前的抗VEGF疗法具有显著的副作用.
- 来自干细胞的细胞外囊泡提供了一种新的治疗策略.
研究的目的:
- 为了研究从人类脱皮的树叶牙衍生的形囊泡 (SHED-apoVs) 的干细胞在缺血视网膜病变的小鼠模型中的治疗潜力.
- 阐明底层机制,包括内皮细胞糖解和PD1/PDL1轴的调节.
主要方法:
- 在氧诱导视网膜病变 (OIR) 的小鼠体内注射SHED-apoVs.
- 视网膜新血管化,血管改造和视觉功能的评估.
- 使用细胞外酸化速率和乳酸试验测量内皮细胞 (EC) 糖分活性.
- 使用lentivirus和中和抗体对PD1/PDL1轴的研究.
主要成果:
- 在OIR小鼠中,ECs有效地吸收了SHED-apoVs.
- SHED-apoVs调节了EC糖解,从而减少了新血管化和改善了血管重塑.
- 确定了PD1/PDL1轴作为一个关键的调解器,apoV携带的PD1与PDL1在低氧EC上相互作用.
- SHED-apoVs抑制了病态血管生成,并促进了血管重塑.
结论:
- SHED-apoVs通过向病态血管生成来治疗缺血性视网膜病变是一种有前途的新策略.
- 治疗效果部分通过通过PD1/PDL1相互作用调节EC糖解来调节.
- 这项研究为病态视网膜新血管化提供了潜在的临床方法.
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