Which Is the Most Suitable and Effective Route of Administration for Mesenchymal Stem Cell-Based Immunomodulation Therapy in Experimental Kidney Transplantation: Endovenous or Arterial?

S. Zonta, M. De Martino, G. Bedino, G. Piotti, T. Rampino, M. Gregorini, F. Frassoni, A. Dal Canton, P. Dionigi, M. Alessiani

Research output: Contribution to journalArticle

Abstract

Immunomodulating cell therapy represents a new perspective for the control of cellular immune responses that determine the occurrence of acute rejection (ACR) in allo-transplantation. Mesenchymal stem cells (MSC) demonstrate immunoregulatory effects by inactivating T-cell components that regulate tissue damage in transplantation models. The presumed mechanism of action is recruitment of cells by a cytokine network. The purpose of this study was to test which route of administartion (intra-arterial vs intravenous) was the most effective route to achieve immunomodulating effects in experimental rat kidney transplantation. Transgenic Sprague-Dawley rats (SD) expressing the enhanced green fluorescent protein (EGFP) at the somatic level were used as MSC donors: Allogeneic Fischer to Lewis grafts (n = 4 per group) were performed in rats after bilateral nephrectomy. In Gr B, 3 × 106 MSCs were infused into the renal graft artery, whereas in Gr C, they were infused into the tail vein. The untreated Gr A were a control group. No immunosuppressive therapy was administered. The animals were sacrificed at day 7 postoperatively. Biochemical analysis for renal function, histological (Banff criteria) and immunohistological (anti-EGFP-Immunoglobulin) analysis were performed on the transplanted animals. In Gr B, functional recovery was more rapid (creatinine: Gr B vs Gr C, P <.05). The inflammatory infiltrate in the graft was less in Gr B vs Gr C, with preservation of tubules, arteries, and glomeruli (P <.01). Intra-arterial infusion of MSCs was more effective to control ACR.

Original languageEnglish
Pages (from-to)1336-1340
Number of pages5
JournalTransplantation Proceedings
Volume42
Issue number4
DOIs
Publication statusPublished - May 2010

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ASJC Scopus subject areas

  • Surgery
  • Transplantation

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