AUTHOR=Hou Jiguang , Zhang Sunfu , Luo Shuang , Zuo Xiao , Ma Fei , Wang Huizhen , Han Pengfei , Zhu Ping , Wang Ning , Hou Xiaoming , Li Jin TITLE=Csf1+ AD-MSCs promote stroke repair by activating the resident microglia JOURNAL=Experimental Biology and Medicine VOLUME=Volume 250 - 2025 YEAR=2025 URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10611 DOI=10.3389/ebm.2025.10611 ISSN=1535-3699 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.