title: Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival.
abstract: Application of mesenchymal stromal cells (MSCs) has been proposed for solid organ transplantation based on their potent immuno-modulatory effects in vitro and in vivo. We investigated the potential of MSCs to improve acceptance of kidney transplants in an MHC-incompatible rat model including isogeneic kidney transplantation (RTx) as control. MSCs were administered i.v. or i.a. at time of transplantation. No immunosuppression was applied. Renal function was monitored by serum-creatinine, histopathology, immunochemistry for graft infiltrating cells and expressions of inflammatory genes. We demonstrated the short-term beneficial effects of MSC injection. In the long term, however, MSC-related life-threatening/shortening events (thrombotic microangiopathy, infarctions, infections) were evident despite decreased T- and B-cell infiltration, lower interstitial inflammation and downregulated inflammatory genes particularly after i.a. MSC injection. We conclude that i.a. MSC administration provides efficient immunomodulation after allogeneic RTx, although timing and co-treatment strategies need further fine-tuning to develop the full potential of powerful cell therapy in solid organ transplantation.
authors.affiliation: Dept. of Hepatobiliary Surgery and Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: martina.koch@uke.de.
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: A
authors.initials: A
authors.lastname: Lehnhardt
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Brunswig-Spickenheier
authors.forename: M
authors.initials: M
authors.lastname: Stolk
authors.forename: V
authors.initials: V
authors.lastname: Bröcker
authors.forename: M
authors.initials: M
authors.lastname: Noriega
authors.forename: M
authors.initials: M
authors.lastname: Seifert
authors.forename: C
authors.initials: C
authors.lastname: Lange
mesh_terms: D064591:Allografts; D000818:Animals; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051381:Rats
keywords: Allograft rejection; HUS; Hpf; Immune modulation; Kidney transplantation; MSCs; Mesenchymal stromal cell; RTx; SCr; Side effect; TMA; hemolytic uremic syndrome; high power field; mesenchymal stromal cells; renal transplantation; serum creatinine; thrombotic microangiopathy