Wharton’s Jelly-Derived Mesenchymal Stem Cells Improve Functional Recovery and Reduce Neuroinflammation Following Experimental Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a severe form of stroke with limited therapeutic options. Mesenchymal stem cells (MSCs) derived from Wharton’s jelly have emerged as a promising therapy due to their neuroprotective and immunomodulatory properties. Here, we investigated the therapeutic effects of Wharton’s jelly-derived MSCs in an experimental model of ICH.

Adult male and female Wistar rats (CEUA A02/24-042/20) underwent stereotaxic intrastriatal injection of collagenase to induce ICH. Twenty-four hours later, animals received MSCs or vehicle by intraperitoneal injection. Motor function was assessed using the rotarod test. Neurodegeneration was evaluated by Fluoro-Jade C staining, while astrocytic and microglial responses were assessed by GFAP and Iba-1 immunoreactivity, respectively. Microglial morphology was also analyzed.

MSC-treated animals of both sexes showed improved motor performance compared with vehicle-treated controls. MSC therapy also reduced neuronal degeneration in the striatum and ipsilateral cortex. Furthermore, GFAP and Iba-1 immunoreactivity were significantly reduced in both regions following treatment. Microglia from MSC-treated animals displayed a more ramified morphology, in contrast to the predominantly amoeboid phenotype observed in controls, suggesting reduced microglial reactivity.

These findings demonstrate that Wharton’s jelly-derived MSC therapy improves motor recovery, reduces neuronal degeneration, and attenuates astrocytic and microglial responses after experimental ICH. The shift toward a more ramified microglial phenotype suggests that MSC treatment promotes a less inflammatory environment, supporting its potential as a therapeutic strategy for hemorrhagic stroke.