Umbilical Cord Stem/Progenitor Cells are able to integrate within the CNS upon injury and to improve the condition of animals suffering from neurodegenerative diseases. However the mecha- nisms by which such phenomena are mediated are unknown. Therefore the main objective of the present work was to understand how a population of umbilical cord progenitor cells isolated from the Wharton Jelly (HUCPVCs), regulates viability, proliferation and different ion of post-natal hippocampal neurons and cortical glial cells. Hippocampal neurons and glial cells were exposed to HUCPVCs conditioned mediums (CMs) (obtained 24, 48, 72 and 96 after 3 days of culture of HUCPVCs) for 1 week. Direct contact co-culture systems were set by using neuron/glial cells feeder layers, on top of which HUCPVCs were platted. Cell viability and proliferation was assessed by MTS test and total protein quantifi- cation. Immunocytochemistry against GFAP (astrocytes), CD11b (microglia), O4 (oligodendrocytes) and HNA (HUCPVCs) was also performed. Cell viability and proliferation experiments re- vealed that HUCPVCs CM obtained for all time points did not cause any deleterious effects on both cell populations when com- pared to the control condition. Immunocytochemistry and total cell counts revealed that HUCPVCs CM triggered an upregulation of the proliferation on astrocytes, oligodendrocytes and differentia- tion of hippocampal neurons. For the latter this was noticed even in the absence of neuronal supplements B27 and FGF-2. Furthermore the co-culture systems revealed that glial cells were inducing HUCPVCs death, attributed to direct cell-to-cell contacts and cell proliferation dependent mechanisms. Noteworthy to mention is that the number of astrocytes and oligodendrocytes increased in the co-culture system, even when HUCPVCs were dying. We believe that the phenomena here in described are related to the release of specific growth factors by HUCPVCs. Future work will focus on the identification of the growth factors involved and consequent crosstalking mechanisms related to the phenomena herein pre- sented.