KMID : 1204720170100020160
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International Journal of Stem Cells 2017 Volume.10 No. 2 p.160 ~ p.168
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Treatment with Allogenic Mesenchymal Stromal Cells in a Murine Model of Systemic Lupus Erythematosus
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Tani Chiara
Vagnani Sabrina Carli Linda Querci Francesca Kuhl Anja A. Spieckermann Simone Cieluch Constanze Pamela Pacini Simone Fazzi Rita Mosca Marta
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Abstract
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Objective: Pre-clinical and uncontrolled studies in patients with systemic lupus erythematosus (SLE) showed that mesenchymal stromal cells (MSCs) have a potential therapeutic role in refractory cases. The optimal therapeutic strategy in these patients remain to be elucidated. Our aim was to test the hypothesis that repeated administrations of 1¡¿106/kg body weight of allogenic MSCs, that is a significantly lower dosage with respect to the fixed 1¡¿106 MSC used in animal models, can be effective in improving the clinical course of a murine SLE model.
Methods: Bone marrow derived MSCs were obtained from 12-week-old C57BL/6J mice. Seventy-five 8 weeks old female NZ mice were randomly assigned to receive via caudal vein the following alternative treatments: 1) single infusion of 106 MSCs/kg body weight at 18 weeks of age (NZs18) or at at 22 weeks of age (NZs22); 2) multiple monthly infusions of 106 MSCs/kg body weight starting at 18 weeks of age (NZM18) or at 22 weeks of age (NZM22); 3) saline infusions (NZc) Fifteen 8 weeks old C57BL/6J mice (Envigo, Huntingdon, UK) were used as untreated controls (C). Weekly, body weight was recorded and twenty-four hour urines were collected by metabolic cages for each animal; proteinuria was detected by dipstick analysis. At sacrifice, peripheral blood samples were collected from mice and anti-dsDNA antibodies were detected by enzyme immunoassorbent assay (ELISA) method using commercial kits. At sacrifice, kidneys were analyzed for histopathology and immunohistochemical analysis for B220, CD4, MPO, CD4+Foxp3, F40/80 infiltration was performed.
Results: Proteinuria occurrence was delayed NZS and NZM mice, no differences were observed in anti-dsDNA autoantibody titer among the groups at the different time-points; at 36 weeks, no significant differences were observed in term of nephritis scores. Inflammatory cells deposition (MPO and F4/80 positive cells) in NZM was significantly higher than in NZ and NZS. An overexpression of B lymphocytes (B220) was found in NZM while T regulatory cells (CD4+ Foxp3+ cells) were reduced in both NZS and NZM with respect to NZc.
Conclusions: Overall, our study failed to show a positive effect of a treatment with murine MSCs in this model and, for some aspects, even deleterious results seem to be observed.
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KEYWORD
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Mesenchymal stromal cells, Systemic lupus erythematosus, Animal model, Lupus nephritis
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