Localization of mesenchymal stromal cells dictates their immune or proinflammatory effects in kidney transplantation

F. Casiraghi, N. Azzollini, M. Todeschini, R. A. Cavinato, P. Cassis, S. Solini, C. Rota, M. Morigi, M. Introna, R. Maranta, N. Perico, G. Remuzzi, M. Noris

Research output: Contribution to journalArticlepeer-review

Abstract

Multipotent mesenchymal stromal cells (MSC) have recently emerged as promising candidates for cell-based immunotherapy in solid-organ transplantation. However, optimal conditions and settings for fully harnessing MSC tolerogenic properties need to be defined. We recently reported that autologous MSC given posttransplant in kidney transplant patients was associated with transient renal insufficiency associated with intragraft recruitment of neutrophils and complement C3 deposition. Here, we moved back to a murine kidney transplant model with the aim to define the best timing of MSC infusion capable of promoting immune tolerance without negative effects on early graft function. We also investigated the mechanisms of the immunomodulatory and/or proinflammatory activities of MSC according to whether cells were given before or after transplant. Posttransplant MSC infusion in mice caused premature graft dysfunction and failed to prolong graft survival. In this setting, infused MSC localized mainly into the graft and associated with neutrophils and complement C3 deposition. By contrast, pretransplant MSC infusion induced a significant prolongation of kidney graft survival by a Treg-dependent mechanism. MSC-infused pretransplant localized into lymphoid organs where they promoted early expansion of Tregs. Thus, pretransplant MSC infusion may be a useful approach to fully exploit their immunomodulatory properties in kidney transplantation. In a murine kidney transplant model, posttransplant MSC infusion causes premature graft dysfunction and fails to prolong graft survival, while pretransplant MSC infusion induces a significant prolongation of kidney graft survival by a regulatory T cell-dependent mechanism.

Original languageEnglish
Pages (from-to)2373-2383
Number of pages11
JournalAmerican Journal of Transplantation
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Graft inflammation
  • in vivo localization
  • kidney transplantation
  • mesenchymal stromal cells
  • mice
  • regulatory T cells

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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