Abstract
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.
Highlights
Mammalian central nervous system (CNS) neurons are not replaced upon lesion and death
We studied the capacity of human Wharton’s jelly mesenchymal stem cells (hWJMSCs) to suppress the proliferation of T cells stimulated by co-culture with allogeneic myeloid dendritic cells, using mixed lymphocyte cultures
At the lowest ratio hWJMSCs: effector T cells (1:100), T cell proliferation was significantly reduced compared to the control co-culture in the absence of hWJMSCs (11% reduction, p < 0.05)
Summary
Mammalian central nervous system (CNS) neurons are not replaced upon lesion and death. Adult stem cells can be isolated from several sources such as bone marrow (BM), dental pulp, adipose tissue, umbilical cord (UC) or placenta. As the other MSC populations from the UC10, hWJMSCs retain the same properties throughout the UC length[11] maximising the use of each cord. They offer the best clinical utility as they have less non-stem cell contaminants, can be generated in large numbers with minimal culture, their derivation is quick and easy to standardize, they are rich in stemness characteristics and have high differentiation potential[12]. HWJMSCs, have an enhanced expression of neurotrophic factors, and a spontaneous tendency toward a neural lineage differentiation compared to MSCs isolated from adult tissues[13,14]
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