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集落刺激因子1基因修饰的脂肪间充质干细胞通过激活内源性小胶质细胞促进中风修复。

Csf1 AD-MSCs promote stroke repair by activating the resident microglia.

作者信息

Hou Jiguang, Zhang Sunfu, Luo Shuang, Zuo Xiao, Ma Fei, Wang Huizhen, Han Pengfei, Zhu Ping, Wang Ning, Hou Xiaoming, Li Jin

机构信息

Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.

Department of Neurosurgery, Third People's Hospital of Chengdu, Chengdu, China.

出版信息

Exp Biol Med (Maywood). 2025 Aug 20;250:10611. doi: 10.3389/ebm.2025.10611. eCollection 2025.

Abstract

The potential of mesenchymal stromal cells (MSCs) in the treatment of hemorrhagic stroke has been demonstrated; however, their clinical efficacy remains inconsistent and further comprehensive studies on their mechanism of action are warranted. In this study, the intracerebral hemorrhage (ICH) rat model was used for intravenous infusion of adipose-derived mesenchymal stromal cells (AD-MSCs) 24 h after modeling. Histopathological techniques and single cell transcriptome sequencing techniques were used to study the mechanism of AD-MSCs promoting the repair of damaged brain tissue. The results indicated that AD-MSCs markedly promote the repair of damaged brain tissues and restored neural function. Single-cell transcriptome sequencing further revealed that this therapeutic effect is specifically through the inhibition of monocyte infiltration in injured brain tissue, promotion of resident microglia proliferation and signaling pathways linked to immune response and neuroprotection. These processes are closely tied to the Csf1 subgroup of AD-MSCs. For acute hemorrhagic stroke, Csf1 AD-MSCs promote the repair of damaged brain tissue by activating resident microglia and inhibiting monocyte infiltration. This study offers novel insights into the mechanisms underlying MSC-based stroke treatment and supports the potential for stable and efficacious MSC therapies.

摘要

间充质基质细胞(MSCs)在治疗出血性中风方面的潜力已得到证实;然而,它们的临床疗效仍不一致,因此有必要对其作用机制进行进一步的全面研究。在本研究中,脑出血(ICH)大鼠模型在建模后24小时用于静脉输注脂肪来源的间充质基质细胞(AD-MSCs)。采用组织病理学技术和单细胞转录组测序技术研究AD-MSCs促进受损脑组织修复的机制。结果表明,AD-MSCs显著促进受损脑组织的修复并恢复神经功能。单细胞转录组测序进一步揭示,这种治疗效果具体是通过抑制损伤脑组织中的单核细胞浸润、促进常驻小胶质细胞增殖以及与免疫反应和神经保护相关的信号通路来实现的。这些过程与AD-MSCs的Csf1亚群密切相关。对于急性出血性中风,Csf1 AD-MSCs通过激活常驻小胶质细胞和抑制单核细胞浸润来促进受损脑组织的修复。本研究为基于MSCs的中风治疗潜在机制提供了新的见解,并支持了稳定有效的MSCs治疗的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9cb/12405005/9d42b7add543/ebm-250-10611-g001.jpg

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