Infusion of autologous bone marrow derived mononuclear stem cells potentially reduces urinary markers in diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Previous studies demonstrated safety and efficacy of autologous bone marrow-derived mononuclear cells (ABM-MNCs) in induced type-1 diabetes mellitus (T1DM) rats. However, the effect of ABM-MNCs on urinary markers of DN in humans is not well studied. We evaluated the therapeutic effect of ABM-MNCs on the urinary markers microalbuminuria (MAU), urinary type-IV collagen and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in T1DM patients with and without nephropathy. This prospective open-label pilot study included 15 patients with T1DM, who had completed 2 visits within 6 months. Patients were divided into two groups according to the presence (DN, n = 7) and absence of nephropathy (T1DM, n = 8). ABM-MNCs were injected at each visit as per study protocol. Routine laboratory data, diabetes tests (fasting serum C-peptide and insulin, glycated hemoglobin, fasting and postprandial glucose), 24-h MAU and urinary type-IV collagen were measured at each visit. uNGAL levels were studied before and after 3days of ABM-MNCs infusion at each visit. Mean age of patients was 29.2 ± 10.4 years, 33% were male, and 27% of the overall group had hypertension. MAU was significantly reduced in the overall group (- 26.0%, p = 0.037), including in DN (- 83.2%, p = 0.021). A short-term significant reduction of uNGAL levels was observed 3days after ABM-MNCs administration during the both the 1st visit (median 13.4 vs. 9.5ng/ml, p = 0.027) and 2nd visit (median 8.8 vs. 6.4ng/ml, p = 0.042) in both groups. However this reduction did not remain significant at the 6-month follow-up. Urinary type-IV collagen did not respond significantly to ABM-MNCs infusion. Infusion of autologous bone marrow-derived mononuclear cells significantly reduced levels of MAU in DN patients. Further studies with larger sample size are needed to confirm these observations.