Therapeutic effect of human umbilical cord mesenchymal stem cells on neonatal rat hypoxic–ischemic encephalopathy

Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, ChinaThe therapeutic potential of umbilical cord blood mesen-chymal stem cells has been studied in several diseases.However, the possibility that human umbilical cord Whar-ton’s jelly-derived mesenchymal stem cells (hUCMSCs)can be used to treat neonatal hypoxic–ischemic encephal-opathy (HIE) has not yet been investigated. This studyfocuses on the potential therapeutic effect of hUCMSCtransplantation in a rat model of HIE. Dermal fibroblastsserved as cell controls. HIE was induced in neonatal ratsaged 7 days. hUCMSCs labeled with Dil were then trans-planted into the models 24 hr or 72 hr post-HIE throughthe peritoneal cavity or the jugular vein. Behavioral testingrevealed that hUCMSC transplantation but not the dermalfibroblast improved significantly the locomotor function vs.vehicle controls. Animals receiving cell grafts 24 hr aftersurgery showed a more significant improvement than at72 hr. More hUCMSCs homed to the ischemic frontal cor-tex following intravenous administration than after intraper-itoneal injection. Differentiation of engrafted cells intoneurons was observed in and around the infarct region.Gliosis in ischemic regions was significantly reduced afterhUCMSC transplantation. Administration of ganglioside(GM1) enhanced the behavioral recovery on the base ofhUCMSC treatment. These results demonstrate that intra-venous transplantation of hUCMSCs at an early stageafter HIE can improve the behavior of hypoxic–ischemicrats and decrease gliosis. Ganglioside treatment furtherenhanced the recovery of neurological function followinghUCMSC transplantation.