Local delivery of neural progenitor cells and nanomaterial improves functional outcome in a rat model of intracerebral hemorrhage

Abstract

Hematoma aspiration reduces hematoma volume and decreases perihematoma edema. The hemorrhagic cavity provides space for local delivery of potential therapeutic agents. A nanomaterial RADA 16-I has been shown to replace the hematoma and reduce ICH-related injury. In this study, the effect of local delivery of neural progenitor cells (NPC) plus the nanomaterial in a rat model of ICH was studied. NPCs were derived from day 13.5 embryos of green fluorescent protein (GFP) transgenic SD rats. ICH was induced by intrastriatal injection of bacterial collagenase IV. Hematoma aspiration was performed at 3.5 h after ICH. The RADA 16-I solution was injected into the cavity immediately following hematoma aspiration. The NPCs were transplanted embedded in the nanomaterial at 3.5 h after ICH or at 2 weeks after ICH. The functional outcome was assessed. The survival and differentiation of the survived NPCs and the underlying mechanism were evaluated. The cells group exhibited better functional performance than the control group. NPCs survived in the brain cavity. More than half of the survived cells remained undifferentiated, while a quarter of the cells differentiated into GFAP positive astrocytes. Only a very small proportion of GFP cells were NeuN positive neurons. The cells group showed a trend toward increased secretion of neurotrophic factors. Local delivery of neural progenitor cells and nanomaterial improves functional outcome. This study may provide evidence for a new therapeutic strategy for ICH.