Functional neurogenic potencies of human umbilical cord blood-derived multipotent stem cells through multiple mechanisms in mice with neurodegerative diseases
Stem cell transplantation in neurodegenerative diseases including Alzheimer’s disease has been reported. In this study, we hypothesized that human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) have the ability to differentiate into functional neurons in the brain. To test this hypothesis, we verifi ed this assumption in a mouse model of Niemann-Pick type C (NPC1-/-) disease using hUCB-MSCs. hUCB-MSCs were transplanted into the hippocampus of asymptomatic mice with NPC1-/- disease. The transplantation resulted in the recovery of motor function and dramatically prolonged the survival of the NPC1-/- mice. Interestingly, many of the transplanted hUCBMSCs showed microtubule associated protein 2-positive cells with electrophysiological function in the brains of the NPC1- /- mice. To examine if the hUCB-MSCs affect endogenous cell survival in the brain, we performed western blotting using mice brains. These results showed that the hUCB-MSCs can activate the Phosphoinositide 3-kinase-Akt-glycogen synthase kinase 3 beta ser9 and JAK2-Stat3 pathways for neuronal survival and regeneration in the brain by secreting functional factors. We concluded that hUCB-MSCs could contribute to extending the life of the NPC1-/-mice with the recovery of motor function by the differentiation into functional active neurons and cell survival signal cascade. Therefore, it is suggested that hUCBMSCs may be applicable in a broad range of neurodegenerative diseases.