Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival

• Published in: Transplant immunology 2013-12, Vol.29 (1), p.43-50
• Main Authors: Koch, M, Lehnhardt, A, Hu, X, Brunswig-Spickenheier, B, Stolk, M, Bröcker, V, Noriega, M, Seifert, M, Lange, C
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Allograft rejection; Allografts; Animals; Disease Models, Animal; Graft Rejection - immunology; Graft Rejection - pathology; Graft Rejection - prevention & control; Graft Survival - immunology; Immune modulation; Kidney Transplantation; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal stromal cell; Rats; Side effect
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2013.08.004

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.