Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 12, Issue 9, Pages 2373-2383Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1600-6143.2012.04115.x
Keywords
Graft inflammation; in vivo localization; kidney transplantation; mesenchymal stromal cells; mice; regulatory T cells
Categories
Funding
- Fondazione ART per la Ricerca sui Trapianti (Milan, Italy)
- Fondazione ARMR through Delegazione ARMR Lugano Canton Ticino
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available