Infusion of autologous bone marrow derived mononuclear stem cells potentially reduces urinary markers in diabetic nephropathy
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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 3 days 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 3 days after ABM-MNCs administration during the both the 1st visit (median 13.4 vs. 9.5 ng/ml, p = 0.027) and 2nd visit (median 8.8 vs. 6.4 ng/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.
KeywordsType-1 diabetes mellitus, nephropathy Autologous bone-marrow derived stem cells Microalbuminuria Urinary neutrophil gelatinase-associated lipocalin
Preliminary results of this study were presented at 53rd ERA-EDTA Congress, May 21–24, 2016, Vienna, Austria and at 52nd ERA-EDTA Congress, May 28– June 1, 2015, London, United Kingdom.
AG, ZT, ST study concept and design. ZT, MA, LK, ZT, OU acquisition of data. AG, AM, MA Analysis and interpretation of data. AG, AM, ZT Drafting of the manuscript. Critical revision of the manuscript for important intellectual content and approval of the final version all authors.
This study is supported by grant N 0104 RK 00133, C03.01 (Title and code of scientific and technical project: Innovative cell technology in regenerative medicine, 0.0634) from the Ministry of Healthcare of Republic of Kazakhstan to JSC National Scientific Medical Research Center (Project timeframe 2013–2015 years).
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interest in this work.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol of this study (protocol No 004/СТ-14; 24th April 2014) was approved by the Ethical Committee of the National Scientific Medical Research Centre.
Informed consent was obtained from all patients. Research involving human participants.
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