Stem cell–mediated tolerance inducing strategies in organ transplantation

Abstract

The scope of possible tools to modulate the recipients immune response towards tolerance induction basically includes deletional and non deletional mechanisms, which are currently targeted by various strategies including monoclonal antibodies, cytokine deviation, chimerism induction and the support of regulating T-cells. Here we summarize the main findings in the field derived from experimental animal studies and currently performed clinical studies. This review focuses to give a clinically relevant overview over relevant tolerance inducing concepts, taking into consideration risk profiles and clinical efficacy associated with specific immunosuppressive regiments currently applied in the clinical setting of transplantation.

Local administration of Mitomycin‐C‐Treated peripheral blood mononuclear cells (PBMCs) prolongs allograft survival in vascularized composite allotransplantation

“…In an allogeneic mice model Casiraghi et al were able to demonstrate that mesenchymal stem cell therapy applied 1 week and 1 day before semi‐allogeneic heart transplantation significantly ameliorates graft survival, whereas only a much shorter extension of graft survival is seen when cells are applied on the day of transplantation . Fändrich et al showed in rat allogeneic heart and kidney transplant model that only a slight prolongation of graft survival results when immunosuppressive cell therapy is being administered postoperatively whereas treatment 5 days prior to transplantation indefinitely prolongs graft survival . Similarly, a postoperative cell therapy regime did not significantly prolong pulmonary allograft survival in pigs .…”

Μελέτη της διαφοροποίησης και της επιβίωσης στελεχιακών προγονικών κυττάρων του ΚΝΣ παρουσία κυτοκινών in vitro

“…Αυτές οι πρωτοποριακές µελέτες παρείχαν έναν µηχανισµό για την ενήλικη νευρογένεση, καλά εδραιωµένο στα πτηνά, που αρχίζει να γίνεται αποδεκτή και στα θηλαστικά, και διέκριναν την πιθανότητα το ΚΝΣ να έχει αναγεννητικές δυνατότητες. 9 ∆είκτες που καθορίζουν τα αρχέγονα προγονικά κύτταρα του ΚΝΣ τώρα αρχίζουν να αναπτύσσονται. Ως εκ τούτου, προσδιορίζονται συνήθως αναδροµικά βάση της συµπεριφοράς τους µετά από την αποµόνωση τους.…”