Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival
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Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival. / Koch, M; Lehnhardt, A; Hu, Xinli; Brunswig-Spickenheier, B; Stolk, M; Bröcker, V; Noriega, M; Seifert, M; Lange, C.
In: TRANSPL IMMUNOL, Vol. 29, No. 1-4, 2013, p. 43-50.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival
AU - Koch, M
AU - Lehnhardt, A
AU - Hu, Xinli
AU - Brunswig-Spickenheier, B
AU - Stolk, M
AU - Bröcker, V
AU - Noriega, M
AU - Seifert, M
AU - Lange, C
N1 - © 2013.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.1016/j.trim.2013.08.004
DO - 10.1016/j.trim.2013.08.004
M3 - SCORING: Journal article
C2 - 23994720
VL - 29
SP - 43
EP - 50
JO - TRANSPL IMMUNOL
JF - TRANSPL IMMUNOL
SN - 0966-3274
IS - 1-4
ER -
