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AB0166 The Effect of a Treatment with Allogenic Mesenchimal Stromal Cells (MSCS) on Urinary Biomarkers in a Mouse Model of Systemic Lupus Erythematosus
  1. C. Tani1,
  2. S. Vagnani1,
  3. L. Carli1,2,
  4. F. Querci1,
  5. M. Mosca1
  1. 1Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa
  2. 2GenOMeC PhD, University of Siena, Siena, Italy

Abstract

Background Urine is a source of suitable biomarkers for Lupus nephritis (LN) because it is easily accessible and can directly reflect the status of local inflammation and damage in the kidney. In recent decades monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) have been proposed as potential biomarkers for renal involvement in patients with systemic lupus erythematosus (SLE).

Objectives The present study is aimed at evaluating the trend of the urinary MCP-1 (uMCP-1) and NGAL (uNGAL) in a mouse model of SLE after administration of a systemic therapy with bone marrow derived allogenic mesenchimal stromal cells (MSCs) at different phases of the disorder and at different dosages.

Methods 35 female New Zealand Black/New Zealand White F1 (NZB/W) mice have been used as model of SLE and 10 C57BL/6J mice have been used as donors of allogenic bone marrow derived MSCs (BMMSCs). NZB/W mouse were divided into the following experimental groups:

  • 5 NZB/W mouse treated with a single MSCs infusion at 20 weeks of age (NZB/W20)

  • 5 NZB/W mouse treated with a single MSCs infusion at 24 weeks of age (NZB/W24)

  • 5 NZB/W mouse treated with a single MSCs infusion at 32 weeks of age (NZB/W32)

  • 5 NZB/W mouse treated with multiple MSCs infusions started at 20 weeks of age (NZB/WM20)

  • 5 NZB/W mouse treated with multiple MSCs infusions started at 24 weeks of age (NZB/WM24)

  • 10 NZB/W mouse not treated as Controls (C).

Urine was weekly collected from mice by metabolic cages; urinary MCP-1 and NGAL were measured with immunoassorbent assay kits (MCP-1, Thermo Scientific; NGAL-2, Boster Biological Technology).

Results In untreated mice uNGAL resulted 38.7±26.7 ng/ml at 18 weeks and it increased from 24 weeks of age (120±3.5 ng/ml) reaching a pick after 35 weeks of age (180.5±42.5 ng/mg). At 24 weeks uNGAL was 32.7±24.6 ng/ml in NZB/W20, 30.4±17 ng/ml in NZB/WM24. At 35 weeks of age uNGAL was 184.6±28.2 ng/ml in NZB/W20, 84.4±27.8 ng/ml in NZB/W24 and 158±66.2 ng/ml in NZB/W32. At 35 weeks of age uNGAL was 152.5±99.5 in NZB/WM20 and 49.5±8 ng/ml in NZB/WM24 (p=0.009 if compared to untreated mice). No differences in uMCP-1 were detected into the different treatment arms if compared to the controls.

Conclusions In our experiments, multiple infusions of allogenic bone marrow derived MSCs were associated with lower urinary levels of NGAL. On the other hand, this treatment does not seem to influence urinary MCP-1 concentrations in this model. Further investigations are ongoing to clarify the possible relationship between MSCs treatment and urinary NGAL in this model of lupus nephritis.

Disclosure of Interest None declared

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