Effect of Timing and Complement Receptor Antagonism on Intragraft Recruitment and Protolerogenic Effects of Mesenchymal Stromal Cells in Murine Kidney Transplantation

Transplantation
Federica CasiraghiGiuseppe Remuzzi

Abstract

Mesenchymal stromal cells (MSCs) have protolerogenic effects in renal transplantation, but they induce long-term regulatory T cells (Treg)-dependent graft acceptance only when infused before transplantation. When given posttransplant, MSCs home to the graft where they promote engraftment syndrome and do not induce Treg. Unfortunately, pretransplant MSC administration is unfeasible in deceased-donor kidney transplantation. To make MSCs a therapeutic option also for deceased organ recipients, we tested whether MSC infusion at the time of transplant (day 0) or posttransplant (day 2) together with inhibition of complement receptors prevents engraftment syndrome and allows their homing to secondary lymphoid organs for promoting tolerance. We analyzed intragraft and splenic MSC localization, graft survival, and alloimmune response in mice recipients of kidney allografts and syngeneic MSCs given on day 0 or on posttransplant day 2. C3a receptor (C3aR) or C5a receptor (C5aR) antagonists were administered to mice in combination with the cells or were used together to treat MSCs before infusion. Syngeneic MSCs given at day 0 homed to the spleen increased Treg numbers and induced long-term graft acceptance. Posttransplant MSC infusion, co...Continue Reading

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Citations

Dec 10, 2019·Current Opinion in Organ Transplantation·Sonia FioriFederica Casiraghi
Jun 9, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Emily R ThompsonColin H Wilson
Jun 25, 2019·Frontiers in Immunology·Manuel Alfredo PodestàFederica Casiraghi
Dec 29, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Federica CasiraghiUNKNOWN MSC-LIVER Study Group
Jan 12, 2021·Molecular Therapy. Methods & Clinical Development·Hiromi Hayashita-KinohTakashi Okada
Mar 2, 2021·Frontiers in Immunology·Manuel Alfredo PodestàFederica Casiraghi
Nov 2, 2020·Transplant International : Official Journal of the European Society for Organ Transplantation·Emily R ThompsonColin H Wilson
Dec 16, 2021·International Journal of Urology : Official Journal of the Japanese Urological Association·Xinning WangRuipeng Jia

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