Mesenchymal Stem Cells From Human Umbilical Cord Regulate The Expression Of Major Histocompatibility Complex In Human Neural Stem Cells And Their Lineages

NEUROSCIENCE LETTERS(2020)

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摘要
hNSCs (human neural stem cells) derived from embryonic tissue and aborted fetal brains are considered to be the most promising candidates for neurodegenerative and other CNS(central nervous system) diseases. However, the most common problem, which limited successful use of these allogeneic hNSC therapy, is immune rejection. Mesenchymal stem cells (MSCs) from human umbilical cord (hUC-MSCs) are receiving increasing attention for their immune-modulatory properties. In the current studies, we firstly investigated the immunogenecity of hNSCs as well as their lineages in cultures with the presence or absence of interferon gamma (IFN gamma), a pro-inflammatory factors. Our data revealed that the majority of hNSCs and astrocytes expressed MHCI (major histocompatibility complex class I) while neurons hardly expressed MHCI (<5%) in the absence of IFN gamma. In addition, neither hNSCs nor neurons expressed MHCII while a subpopulation (about 18 %) of astrocytes expressed MHCII without IFN gamma stimulation. However, the addition of IFN gamma in cultures significantly increased the expressions of MHCII on hNSCs and astrocytes. However, IFN gamma did not affect the expression of MHCI on hNSCs and astrocytes. We then investigated whether hUC-MSCs had the capacity of regulating the immunogenecity of hNSCs as well as their lineages in a co-culture system. We found that hUC-MSCs did not affect the expression of MHCI on hNSCs and their lineages, however, these cells were able to significantly inhibit the IFN gamma-induced up-regulation of MHCII on hNSCs and astrocytes (p < 0.001). Thus, our results suggest that hUC-MSCs may serve as potentially useful modulators to reduce the immunogenicity of allogeneic hNSCs in clinical application.
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关键词
MHCI, MHCII, Human neural stem cells, Mesenchymal stem cells from human umbilical cords, Interferon gamma
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