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.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Koch M,Lehnhardt A,Hu X,Brunswig-Spickenheier B,Stolk M,Bröcker V,Noriega M,Seifert M,Lange C

doi

10.1016/j.trim.2013.08.004

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

43-50

issue

1-4

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(13)00068-3

journal_volume

29

pub_type

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