Mesenchymal stem cell transplantation improves motor recovery accompanied by region-specific transcriptomic responses following intracerebral hemorrhage in rats

Background Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapeutic strategy for intracerebral hemorrhage (ICH); however, the molecular mechanisms underlying its restorative effects remain poorly understood. This study evaluates the therapeutic effects of MSC transplantation following experimental ICH using bulk RNA sequencing, offering a comprehensive transcriptomic perspective.Methods Adult Sprague-Dawley (SD) rats were assigned to Sham, ICH, and ICH plus MSC (ICH + MSC) groups. ICH was induced by collagenase injection into the striatum adjacent to the internal capsule. Two weeks after ICH induction, MSCs were transplanted into the lesion site, and brain tissue from the lesion hemisphere was collected three weeks later. Sham animals received phosphate-buffered saline (PBS). Motor recovery was assessed using the modified neurological severity score and the cylinder test. RNA sequencing and quantitative RT-PCR were performed to characterize transcriptional alterations associated with MSC treatment.Results MSC transplantation significantly reversed the impaired motor function induced by ICH. Transcriptomic analysis revealed that MSC transplantation predominantly enriched biological processes associated with neurite development, synaptic organization, and synaptic transmission. PROGENy pathway analysis predicted increased PI3K-related pathway activity in the lesion. Furthermore, MSC transplantation was associated with elevated cortical expression of neurotrophins and plasticity-associated transcripts.Conclusions MSC transplantation promotes functional recovery after ICH and induces a distinct transcriptional shift from injury-associated responses toward regenerative plasticity, associated with engagement of PI3K-related signaling. These findings provide comprehensive insight into MSC-mediated brain repair and evidence for its therapeutic potential in ICH.