Journal
TRANSPLANT IMMUNOLOGY
Volume 29, Issue 1-4, Pages 43-50Publisher
ELSEVIER
DOI: 10.1016/j.trim.2013.08.004
Keywords
Mesenchymal stromal cell; Kidney transplantation; Allograft rejection; Immune modulation; Side effect
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Funding
- Novartis Pharma, Germany
- BCRT (BMBF) [1315848A]
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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 Iv. 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. (C) 2013 Elsevier B.V. All rights reserved.
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