Autologous bone marrow-derived mesenchymal stem cells for interstitial fibrosis and tubular atrophy: a pilot study

Abstract

Background Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. Methods From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. Results At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-β1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. Conclusion Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-β1: transforming growth factor β1; CTGF: connective tissue growth factor