Histological improvement following administration of autologous bone marrow-derived mesenchymal stemcells for alcoholic cirrhosis: a pilot study

Histological improvement following administration of autologous bone marrow-derived mesenchymal stemcells for alcoholic cirrhosis: a pilot study
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DOI:
10.1111/liv.12218
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发表时间:
2014-01-01
影响因子:
6.7
通讯作者:
Kim, Yong Man
Kim, Yong Man
中科院分区:
医学2区
文献类型:
--
作者:
Jang, Yoon Ok;Kim, Young Ju;Kim, Yong Man

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背景在实验模型中,骨髓间充质干细胞(BM-MSCs)具有向肝细胞分化的能力,并具有抗肝纤维化的作用。本研究的目的是阐明骨髓间充质干细胞在酒精性肝硬变患者中的抗纤维化作用,作为II期临床试验。方法入选12例酒精性肝硬变患者(男11例,女1例),均为基线活检证实的酒精性肝硬变患者,戒酒至少6个月。从患者的骨髓中分离BM-MSCs并扩增1个月,然后在第4周和第8周经肝动脉注射5x10(7)细胞两次。一名患者因摄入酒精而退出治疗。最后,11例患者在第二次注射后12周完成随访活检和实验室检查。结果根据Laennec纤维化系统,11例患者中有6例组织学改善(54.5%)。经BM-MSCs治疗后,10例患者的Child-Pugh评分改善(90.9%),转化生长因子-1、1型胶原和-平滑肌肌动蛋白水平(实时定量逆转录-聚合酶链式反应)显著降低(P
BackgroundIn experimental models, bone marrow-derived mesenchymal stem cells (BM-MSCs) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects. However, there have been no studies in humans with alcoholic cirrhosis.AimThe aim of this study was to elucidate the antifibrotic effect of BM-MSCs in patients with alcoholic cirrhosis, as a phase II clinical trial.MethodsTwelve patients (11 males, 1 female) with baseline biopsy-proven alcoholic cirrhosis who had been alcohol free for at least 6months were enrolled. BM-MSCs were isolated from each patient's BM and amplified for 1month, and 5x10(7) cells were then injected twice, at weeks 4 and 8, through the hepatic artery. One patient was withdrawn because of ingestion of alcohol. Finally, 11 patients completed the follow-up biopsy and laboratory tests at 12weeks after the second injection. The primary outcome was improvement in the patients' histological features.ResultsAccording to the Laennec fibrosis system, histological improvement was observed in 6 of 11 patients (54.5%). The Child-Pugh score improved in ten patients (90.9%) and the levels of transforming growth factor-1, type 1 collagen and -smooth muscle actin significantly decreased (as assessed by real-time reverse transcriptase polymerase chain reaction) after BM-MSCs therapy (P