Efficacy of cell sheet transplantation of olfactory neural-progenitor cells in a canine model of intracranial hemorrhage

Abstract

Cell-based therapy for intracerebral hemorrhage (ICH) has a substantial therapeutic potential. However, methods to effectively deliver, and improve survival and differentiation of stem cells have not been established. We developed a cell sheet for neural stem cells, with successful application in a canine ICH model. We designed a composite cell sheet made of neural progenitors derived from human olfactory epithelium and human adipose tissue–derived stroma cells. We also generated a canine model of ICH, by manually injecting and then infusing autologous blood under an arterial pressure. We transplanted cells sheets (cell sheet group) or saline (control group) at the cortex over the hematoma, at 2 weeks from ICH induction. At 4 weeks from the cell transplantation, cell survival, migration and differentiation were evaluated. Hemispheric atrophy and neurobehavioral recovery were also compared between two groups. The cell sheet was rich of extracellular matrices and highly expressed neuroprotective cytokines, as well as marker for neuron development. The transplanted cells successfully survived for 4 weeks, and the significant portion of them migrated in the perihematomal site and differentiated to neurons and pericytes. Transplantation of cell sheets alleviated hemorrhage-related hemispheric atrophy and modestly improved functional recovery. In conclusion, cell sheet delivers neural stem cells directly to the target area with increased cell survival and differentiation, as well as effectively reduce the hemispheric atrophy and modestly improves functional recovery.