Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients
| Autor: | Behzad Einollahi, Atieh Makhlough, Soroosh Shekarchian, Nasser Aghdami, Tina Bolurieh, Seyedeh Esmat Hosseini, Hossein Baharvand, Neda Jaroughi, Reza Moghadasali |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine 030232 urology & nephrology Medicine (miscellaneous) Blood Pressure Kidney chemistry.chemical_compound 0302 clinical medicine Chronic kidney disease lcsh:QD415-436 lcsh:R5-920 education.field_of_study Middle Aged Polycystic Kidney Autosomal Dominant medicine.anatomical_structure Tolerability Creatinine Molecular Medicine Female lcsh:Medicine (General) Glomerular Filtration Rate Adult medicine.medical_specialty Endpoint Determination Population Urology Autosomal dominant polycystic kidney disease Renal function Bone Marrow Cells Mesenchymal Stem Cell Transplantation Transplantation Autologous Biochemistry Genetics and Molecular Biology (miscellaneous) lcsh:Biochemistry 03 medical and health sciences Bone marrow mesenchymal stromal cells medicine Humans Adverse effect education Demography business.industry Research Mesenchymal Stem Cells Cell Biology medicine.disease Surgery Transplantation 030104 developmental biology chemistry Bone marrow business Follow-Up Studies |
| Zdroj: | Stem Cell Research & Therapy, Vol 8, Iss 1, Pp 1-11 (2017) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| Popis: | 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 m2. Patients received autologous cultured BMMSCs (2 × 106 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 m2 1 year before cell infusion declined to 26.7 ± 3.1 ml/min/1.73 m2 at baseline (P = 0.03) and 25.8 ± 6.2 ml/min/1.73 m2 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. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0557-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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