Mesenchymale Stammzellen beeinflussen das Transplantatüberleben unterschiedlich in Abhängigkeit einer immunsuppressiven Therapie

Abstract

Mesenchymal stem cells (MSC) are promising candidates to induce tolerance in solid organ transplantation. We have previously shown that MSC can prolong heart graft survival in a rat transplantation model [1]. To elucidate the mechanisms driving MSC facilitated solid organ survival we analyzed transplanted animals at different time points. More activated leukocytes were detected in the spleens (CD8+CD28+ cells) and in abdominal lymph nodes (CD4+CD28+ cells) of animals receiving donortype MSC without further treatment indicating that allogeneic MSC sensitize recipients. OX62+ dendritic cells of MSC treated animals express less costimulatory molecules (CD80 and CD86) in spleens and abdominal lymph nodes suggesting that MSC induce a potentially tolerogenic phenotype in dendritic cells. Downregulation of costimulatory molecules in dendritic cells does not depend on application of MPA. Activated leukocytes decrease rapidly over time in abdominal lymph nodes and spleens (most notably CD8+CD28+ cells) indicating loss off effector T cells in animals receiving MSC and MPA. We hypothesize that pre-activated effector T cells are preferentially eliminated by induction of necrosis after application of MPA.