AB0198 Biological properties of urine-stem cells and therapeutic effect on systemic sclerosis fibrosis
Authors: Y. Yang, A. Xiong, Q. Zhang, Y. Luo, Q. Xie, Y. Liu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Because of the lack of effective treatment of systemic sclerosis (SSc), cellular therapy is considered as a salvage option.<sup>1–4</sup> Mesenchymal stem cells (MSCs) are gaining attentions in the field of cell therapy of SSc. However, current isolation methods of MSCs are all invasive and challenging.<sup>5</sup> Some studies have reported the isolation from urine recently, and definition of urine-derived stem cells (USCs).<sup>6</sup> The collection of USCs is noninvasive that could be a desired resource of MSC. So far, the information of therapeutic effect on SSc is limited. <h3>Objectives</h3> We aimed to explore the biological characterizations of USCs and investigate the therapeutic effect on murine SSc model. <h3>Methods</h3> USCs were isolated and cultivated from sterile urine samples of healthy adult individuals. The related cell markers were examined by flow cytometry. The differentiation potentials were observed in adipogenic, osteogenic and chondrogenic medium, respectively. SSc murine models were conducted by daily intradermal injections of bleomycin and were further divided as treated and untreated group. Also, the healthy control group was conducted by daily injection of phosphate buffered saline (PBS). Treated group received an infusion of 2.5 × 10<sup>5</sup> USCs in the tail vein twice in one week after the 3 week modelling. Skin samples were obtained one week after the treatment. Hematoxylin-eosin and Masson staining were accomplished to observe the skin thickness and the hydroxyproline content was detected by hydroxyproline kit. The relative expression of collagen type I alpha 1 chain (Col1-a1), alpha-smooth muscle actin (α-SMA), and fibronectin 1(Fn-1) were detected by real-time quantitative PCR. <h3>Results</h3> The morphology of USCs was spindle-shaped. They express CD73, CD90, and CD105 but CD34, CD45, CD19, CD11b, or HLA-DR. USCs possessed the abilities to differentiate into adipocytes, osteoblasts, and chondrocytes. In USCs treated group, the skin thickness(p=0.031) (Figure1A), the deposition of collagen in HE and Masson trichrome-staining (p=0.007) (Figure1B), and Col1-a1 gene expression(p=0.010) (Figure1C) were significantly reduced in comparison with untreated group and were close to healthy controls. <h3>Conclusions</h3> USCs can be isolated from adult sterile urine. They possess the multipotent differentiation abilities and displays a therapeutic effect on bleomycin-induced skin fibrosis and collagen synthesis. <h3>References</h3> [1] Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med2009;360:1989–2003. [2] Verrecchia F, Laboureau J, Verola O, et al. Skin involvement in scleroderma-where histological and clinical scores meet. Rheumatology2007;46:833–841. [3] Fleming JN, Nash RA, McLeod DO, et al. Capillary regeneration in scleroderma: Stem cell therapy reverses phenotype?PLoS One2008;3:e1452. [4] Aschwanden M, Daikeler T, Jaeger KA, et al. Rapid improvement of nailfold capillaroscopy after intense immunosuppression for systemic sclerosis and mixed connective tissue disease. Ann Rheum Dis2008;67:1057–1059. [5] Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy2005;7:36–45. [6] Zhang Y, McNeill E, Tian H, et al. Urine derived cells are a potential source for urological tissue reconstruction [J]. J Urol2008;180:2226–2233. <h3>Disclosure of Interest</h3> None declared