Placenta-derived mesenchymal stem cells attenuate acute brain injury and neuroinflammation after intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and limited treatment options. This study evaluated the safety and therapeutic potential of human placenta-derived mesenchymal stem cells (PD-MSCs) in acute ICH. PD-MSCs were isolated, characterized, and assessed for tumorigenicity by subcutaneous implantation in nude mice. Acute ICH was induced in rats by collagenase injection, followed by in situ PD-MSC transplantation. Neurological function, brain water content, and hematoma volume were evaluated, and perihematomal biological changes were examined using immunofluorescence staining, ELISA, and transcriptomic sequencing. PD-MSCs displayed typical mesenchymal stem cell characteristics and showed no evidence of tumorigenicity under the present experimental conditions. In ICH rats, PD-MSC transplantation reduced brain edema and hematoma volume and partially improved neurological outcomes compared with those in untreated controls. PD-MSC treatment also modulated astrocytic responses, as reflected by altered glial fibrillary acidic protein expression and astrocyte morphology, and decreased the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α. Transcriptomic analysis indicated that PD-MSCs influenced inflammation-related and immune-regulatory pathways in perihematomal tissues. AKR1B1, SNAI2, and ADGRE5 were identified as candidate genes potentially associated with PD-MSC-mediated responses after ICH. These findings provide preliminary evidence that PD-MSCs are nontumorigenic and may attenuate acute brain injury after ICH, although longer follow-up, expanded behavioral testing, dose optimization, and mechanistic validation are needed to confirm their long-term safety and therapeutic efficacy. SIGNIFICANCE STATEMENT: Acute intracerebral hemorrhage lacks effective therapeutic options, and secondary neuroinflammatory injury contributes substantially to neurological deterioration. This study provides preliminary evidence that placenta-derived mesenchymal stem cells may attenuate acute brain injury and modulate inflammation-associated responses after experimental intracerebral hemorrhage, supporting further investigation of placenta-derived mesenchymal stem cell-based therapeutic strategies for hemorrhagic stroke.