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Syngeneic, in contrast to allogeneic, mesenchymal stem cells have superior therapeutic potential following spinal cord injury

ABSTRACT: We evaluated the importance of histocompatibility of transplanted MSCs in terms of therapeutic potential. Mouse syngeneic MSCs or allogeneic MSCs were transplanted following SCI in mouse. In this study we found that syngeneic, but not allogeneic, MSCs alternatively activated macrophages resulting in a down-regulation of pro-inflammation. Syngeneic MSCs also had a general suppressive effect on the immune response as compared to allogeneic MSCs. Additionally, syngeneic, but not allogeneic, MSCs significantly enhanced the recovery of hind limb function. In this study we show that the histocompatibility of transplanted MSCs is of importance for their therapeutic potential.

ORGANISM(S): Mus musculus

PROVIDER: GSE139227 | GEO | 2019/10/23

REPOSITORIES: GEO

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Project description:Microarray analyses provide a powerful approach to identify gene expression alterations following kidney transplantation. However, the heterogeneity of human kidney transplant specimens and the variation in sample preparation precludes conclusions regarding the underlying mechanisms of the observed alterations. We used a well defined experimental rat kidney transplantation model with consistent transplant and sample preparation procedures to analyze genome wide changes in gene expression after syngeneic (sTX) and allogeneic transplantation (aTX) four days after transplantation. Both interventions were associated with dramatic changes in gene expression. Genes and Pathways related to immune response were extremely up regulated after aTX. Several of the up regulated genes have been described by other groups and we are able to proof this in one study. But several genes are reported for the first time to be up regulated in expression after renal aTX. The function of these genes in acute rejection process has to be evaluated. On the other hand the up regulation of regulatory or protective genes indicates that regulatory mechanism are activated after aTX trying to down regulate the immune response or protect the tissue against the immune system. The study is capable to serve as a representative study in aTX mediated gene expression by covering the known transcriptional changes reported by other groups and identification of novel markers and pathways. Further analysis of the duplicated datasets by other groups can help for a better understanding of the mechanisms mediated by acute rejection and thereby increase the therapeutic threatment. Experiment Overall Design: Male LewisâBrown-Norway (LBN) and Lewis (LEW) rats were used in the present study. All recipients were bilaterally nephrectomized immediately before donor kidney TX. In brief, the left kidney including ureter, renal artery, a piece of aorta and renal vein was transplanted into the recipient. For the allogeneic TX (aTX) model, kidneys of LBN-rats (n=5) were transplanted into LEW-rats and for the syngeneic TX (sTX) model kidneys from LBN-rats (n=5) were transplanted into LBN-rats. The LBN-into-Lewis model leads to marked histological changes typical for acute transplant rejection. The second kidney of the LBN-donors (n=5) served as controls.

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Syngeneic, in contrast to allogeneic, mesenchymal stem cells have superior therapeutic potential following spinal cord injury

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