Mesenchymal stem cell (MSC) transplantation is emerging as an ideal tool to restore the wounded central nervous system (CNS). MSCs isolated from extra-embryonic tissues have some advantages compared to MSCs derived from adult ones, such as an improved proliferative capacity, life span, differentiation potential and immunomodulatory properties. In addition, they are more immunoprivileged, reducing the probability of being rejected by the recipient. Umbilical cords (UCs) are a good source of MSCs because they are abundant, safe, non-invasively harvested after birth and, importantly, they are not encumbered with ethical problems. Here we show that the intravitreal transplant of Wharton´s jelly mesenchymal stem cells isolated from three different human UCs (hWJMSCs) delays axotomy-induced retinal ganglion cell (RGC) loss. In vivo, hWJMSCs secrete anti-inflammatory molecules and trophic factors, the latter alone may account for the elicited neuroprotection. Interestingly, this expression profile differs between naive and injured retinas, suggesting that the environment in which the hWJMSCs are modulates their secretome. Finally, even though the transplant itself is not toxic for RGCs, it is not innocuous as it triggers a transient but massive infiltration of Iba1+cells from the choroid to the retina that alters the retinal structure.