自体骨髓间充质基质细胞在常染色体显性多囊肾病患者中的安全性和耐受性
Safety and tolerability of autologous bone marrow mesenchymal stromal cells in ADPKD patients.
作者信息
Makhlough Atieh, Shekarchian Soroosh, Moghadasali Reza, Einollahi Behzad, Hosseini Seyedeh Esmat, Jaroughi Neda, Bolurieh Tina, Baharvand Hossein, Aghdami Nasser
机构信息
Department of Nephrology, Molecular and Cell Biology Research Center, Sari University of Medical Sciences, Sari, Iran.
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
出版信息
Stem Cell Res Ther. 2017 May 23;8(1):116. doi: 10.1186/s13287-017-0557-7.
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. Patients received autologous cultured BMMSCs (2 × 10 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 1 year before cell infusion declined to 26.7 ± 3.1 ml/min/1.73 m at baseline (P = 0.03) and 25.8 ± 6.2 ml/min/1.73 m 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.
背景
常染色体显性遗传性多囊肾病（ADPKD）是一种遗传性纤毛病疾病，其特征为多个器官中囊肿进行性形成和增大。肾脏尤其易受影响，患者最终可能发展为终末期肾病（ESRD）。我们推测骨髓间充质基质细胞（BMMSCs）具有肾趋向性，可能通过抗凋亡、抗纤维化和抗炎作用改善肾功能。在本研究中，我们旨在评估ADPKD患者输注BMMSCs的安全性和耐受性。
方法
我们进行了一项单臂I期临床试验，随访12个月。本研究纳入了6例符合条件的ADPKD患者，其估计肾小球滤过率（eGFR）为25 - 60 ml/min/1.73m²。患者按照我们的输注方案通过肘静脉接受自体培养的BMMSCs（2×10⁶细胞/kg）。我们在随访期间调查安全性问题和肾功能，并将结果与基线及干预前1年进行比较。
结果
无患者失访。随访12个月后，我们未观察到与细胞相关的不良事件（AE）和严重不良事件（SAE）。细胞输注前1年的平均eGFR值为33.8±5.3 ml/min/1.73m²，基线时降至26.7±3.1 ml/min/1.73m²（P = 0.03），12个月随访时为25.8±6.2 ml/min/1.73m²（P = 0.62）。输注前1年的平均血清肌酐（SCr）水平为2±0.3 mg/dl，基线时升至2.5±0.4 mg/dl（P = 0.04），12个月随访时为2.5±0.6 mg/dl（P = 0.96）。这表明SCr在这两个时期（输注前12个月至基线，输注后12个月至基线）的差异有显著变化（P = 0.05），但eGFR无显著变化（P = 0.09）。
结论
本试验证明了自体BMMSCs静脉移植的安全性和耐受性。ADPKD患者中BMMSCs的疗效应在更大规模人群的随机安慰剂对照试验中进行研究，我们计划开展此项研究。
试验注册
ClinicalTrials.gov，NCT02166489。于2014年6月14日注册。
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