Journal Article

Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients

Hosseini, Seyedeh Esmat, Makhlough, Atieh, Bolurieh, Tina, Moghadasali, Reza, Einollahi, Behzad, Jaroughi, Neda, Baharvand, Hossein, Aghdami, Nasser, Shekarchian, Soroosh

2017

Overview

Background Autosomal dominant polycystic kidney disease (ADPKD) is a genetic ciliopathy disease characterized by progressive formation and enlargement of cysts in multiple organs. The kidneys are particularly affected and patients may eventually develop end-stage renal disease (ESRD). We hypothesize that bone marrow mesenchymal stromal cells (BMMSCs) are renotropic and may improve kidney function via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. In this study, we aim to assess the safety and tolerability of a BMMSC infusion in ADPKD patients. Methods We performed a single-arm phase I clinical trial with a 12-month follow-up. This study enrolled six eligible ADPKD patients with an estimated glomerular filtration rate (eGFR) of 25–60 ml/min/1.73 m 2 . Patients received autologous cultured BMMSCs (2 × 10 6 cells/kg) through the cubital vein according to our infusion protocol. We investigated safety issues and kidney function during the follow-up visits, and compared the findings to baseline and 1 year prior to the intervention. Results There were no patients lost to follow-up. We observed no cell-related adverse events (AE) and serious adverse events (SAE) after 12 months of follow-up. The mean eGFR value of 33.8 ± 5.3 ml/min/1.73 m 2 1 year before cell infusion declined to 26.7 ± 3.1 ml/min/1.73 m 2 at baseline ( P  = 0.03) and 25.8 ± 6.2 ml/min/1.73 m 2 at the 12-month follow-up visit ( P  = 0.62). The mean serum creatinine (SCr) level of 2 ± 0.3 mg/dl 1 year before the infusion increased to 2.5 ± 0.4 mg/dl at baseline ( P  = 0.04) and 2.5 ± 0.6 mg/dl at the 12-month follow-up ( P  = 0.96). This indicated significant changes between the differences of these two periods (12 months before infusion to baseline, and 12 months after infusion to baseline) in SCr ( P  = 0.05), but not eGFR ( P  = 0.09). Conclusions This trial demonstrated the safety and tolerability of an intravenous transplantation of autologous BMMSCs. BMMSC efficacy in ADPKD patients should be investigated in a randomized placebo-controlled trial with a larger population, which we intend to perform. Trial registration ClinicalTrials.gov, NCT02166489 . Registered on June 14, 2014.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Apoptosis / Autografts / Autosomal dominant polycystic kidney disease / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Blood Pressure / Bone marrow / Bone Marrow Cells - cytology / Bone marrow mesenchymal stromal cells / Cell Biology / Chronic kidney disease / Chronic kidney failure / Clinical trials / Creatinine / Creatinine - blood / Cysts / Demography / Development and progression / End-stage renal disease / Endpoint Determination / Epidermal growth factor receptors / Family medical history / Female / Follow-Up Studies / Genetic aspects / Glomerular Filtration Rate / Hepatitis / HIV / Human immunodeficiency virus / Humans / Inflammation / Intravenous administration / Kidney - pathology / Kidney - physiopathology / Kidney diseases / Kidney transplantation / Kinases / Laboratories / Life Sciences / Male / Mesenchymal Stem Cell Transplantation - adverse effects / Mesenchymal stem cells / Mesenchymal Stromal Cells - cytology / Mesenchyme / Middle Aged / Nephrology / Pathogenesis / Polycystic kidney / Polycystic kidney disease / Polycystic Kidney, Autosomal Dominant - blood / Polycystic Kidney, Autosomal Dominant - physiopathology / Polycystic Kidney, Autosomal Dominant - therapy / Regenerative Medicine/Tissue Engineering / Rodents / Stem Cells / Stromal cells / Transplantation / Transplantation, Autologous - adverse effects