修改MSCs与aHSCs向质pPB,以提高肝纤维化治疗疗效
Mengqin Yuan1, Zhengrong Yin2, Zheng Wang3
1Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, Wuhan 430000, China; Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Clinical Research Center for Medical Imaging in Hubei Province, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
Biomaterials
|April 6, 2025
概括
工程化介质干细胞 (MSCs) 通过与激活的肝星细胞 (aHSCs) 结合来向肝纤维化. 这种非遗传方法增强了细胞输送,促进了肝脏的修复,以改善纤维化治疗.
科学领域:
- 再生医学是一种再生医学.
- 细胞疗法细胞疗法
- 生物医学工程 生物医学工程
背景情况:
- 介酶干细胞 (MSCs) 在肝纤维化治疗方面表现有前途.
- 挑战包括不良的定位和在受伤地点保留MSC.
- 激活的肝星细胞 (aHSCs) 驱动肝纤维化并表达PDGFRB.
研究的目的:
- 在肝纤维化中设计MSC来增强对激活性肝星细胞 (aHSC) 的定位.
- 开发一种非遗传表面修饰策略,以改善MSC的交付.
- 在肝纤维化小鼠模型中评估工程MSCs的治疗疗效.
主要方法:
- 通过通过DMPE-PEG-pPB (DPP) 通过pPB质进行表面修饰的工程MSC (pPB-MSC).
- 在修改后评估MSC活力,分化和膜功能.
- 评估了pPB-MSC与aHSCs的结合 in vitro和肝脏积累 in vivo使用TAA诱导的纤维化小鼠成像.
主要成果:
- pPB 修改保留了 MSC 的功能.
- 在纤维化小鼠中,pPB-MSCs对aHSCs的结合增强,肝脏积累更大.
- pPB-MSCs降低了原沉积,抑制了α-SMA+ HSCs,并使肝酶正常化 (ALT/AST).
结论:
- 非遗传MSC表面工程可以改善向纤维化肝组织的目标.
- pPB-MSCs促进肝脏再生,抑制EMT,并调节免疫反应.
- 这一策略为肝纤维化细胞治疗提供了一个临床可翻译的平台.
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