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Clin J Am Soc Nephrol. 2011 Feb;6(2):412-22. doi: 10.2215/CJN.04950610. Epub 2010 Oct 7.

Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility.

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  • 1Transplant Research Center Chiara Cucchi de Alessandri e Gilberto Crespi, Department of Immunology and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Parco Scientifico Tecnologico Kilometro Rosso, via Stezzano 87, 24126 Bergamo, Italy.

Abstract

BACKGROUND AND OBJECTIVES:

Mesenchymal stromal cells (MSCs) abrogate alloimmune response in vitro, suggesting a novel cell-based approach in transplantation. Moving this concept toward clinical application in organ transplantation should be critically assessed.

DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS:

A safety and clinical feasibility study (ClinicalTrials.gov, NCT00752479) of autologous MSC infusion was conducted in two recipients of kidneys from living-related donors. Patients were given T cell-depleting induction therapy and maintenance immunosuppression with cyclosporine and mycophenolate mofetil. On day 7 posttransplant, MSCs were administered intravenously. Clinical and immunomonitoring of MSC-treated patients was performed up to day 360 postsurgery.

RESULTS:

Serum creatinine levels increased 7 to 14 days after cell infusion in both MSC-treated patients. A graft biopsy in patient 2 excluded acute graft rejection, but showed a focal inflammatory infiltrate, mostly granulocytes. In patient 1 protocol biopsy at 1-year posttransplant showed a normal graft. Both MSC-treated patients are in good health with stable graft function. A progressive increase of the percentage of CD4+CD25highFoxP3+CD127- Treg and a marked inhibition of memory CD45RO+RA-CD8+ T cell expansion were observed posttransplant. Patient T cells showed a profound reduction of CD8+ T cell activity.

CONCLUSIONS:

Findings from this study in the two patients show that MSC infusion in kidney transplant recipients is feasible, allows enlargement of Treg in the peripheral blood, and controls memory CD8+ T cell function. Future clinical trials with MSCs to look with the greatest care for unwanted side effects is advised.

PMID:
20930086
[PubMed - indexed for MEDLINE]
PMCID:
PMC3052234
Free PMC Article
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