Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell.

Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell.
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DOI:
10.1016/j.reth.2016.12.001
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发表时间:
2017-06
影响因子:
4.3
通讯作者:
Kaneko S
Kaneko S
中科院分区:
工程技术3区
文献类型:
--
作者:
Sakai Y;Takamura M;Seki A;Sunagozaka H;Terashima T;Komura T;Yamato M;Miyazawa M;Kawaguchi K;Nasti A;Mochida H;Usui S;Otani N;Ochiya T;Wada T;Honda M;Kaneko S

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脂肪组织基质细胞含有大量的间充质干细胞。因此,它们在各种受损器官再生中的应用引起了广泛关注。我们设计了一项临床研究,以探讨新鲜分离的自体脂肪组织来源的基质/干(再生)细胞(ADRC)治疗肝硬化,并在4例肝硬化患者中进行治疗。从通过抽脂法获得的自体皮下脂肪组织中分离ADRC,然后使用Celution系统脂肪组织解离装置。主要终点是治疗后一个月的安全性评估。我们还表征了所获得的ADRCs。2例C型肝硬化,1例非酒精性脂肪性肝炎肝硬化,1例B型肝硬化。在新鲜分离的ADRC输注后的1个月研究期间未观察到严重不良事件。在此期间,以及在随后的随访期间,2例患者约1年,另1例患者约6个月,血清白蛋白浓度保持或改善。肝再生相关因子,即肝细胞生长因子和白细胞介素-6,在所有患者ADRC治疗后1天升高。将获得的新鲜分离的ADRC在培养物中扩增,发现其表达间充质干细胞标志物。ADRCs的基因表达谱分析显示涉及炎症特征,表明所获得的ADRCs的特征与免疫调节生物学效应有关。这项使用ADRC治疗肝硬化的临床研究被证明是安全可行的,并且可以在未来进一步研究肝硬化的再生/修复。脂肪基质细胞治疗肝硬化的临床研究。自体脂肪组织来源的基质/干细胞(再生)细胞通过肝内动脉输注给肝硬化患者。所获得的脂肪组织来源的基质细胞显示含有间充质干细胞。
Adipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention. We designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients. ADRCs were isolated from autologous subcutaneous adipose tissue obtained by the liposuction method, followed with use of the Celution system adipose tissue dissociation device. The primary endpoint is assessment of safety one month after treatment. We also characterized the obtained ADRCs. Two patients had type C cirrhosis, one had nonalcoholic steatohepatitis-cirrhosis, and one had type B cirrhosis. No serious adverse events were observed during the 1-month study period after freshly isolated ADRC infusion. Serum albumin concentrations were maintained or improved during this period as well as during the succeeding follow-up of approximately 1 year in two patients and 6 months in another patient. Liver regeneration-related factors, namely hepatocyte growth factor and interleukin-6, were elevated 1 day after ADRC treatment in all patients. The obtained freshly isolated ADRCs were expanded in culture and found to express mesenchymal stem cell markers. Gene expression profile analysis of ADRCs was shown to involve inflammatory features, suggesting that characteristics of the obtained ADRCs were related to immunomodulatory biological effects. This clinical study treatment for liver cirrhosis using ADRCs was proven to be safely conductible, and can be further investigated in future for regeneration/repair of liver cirrhosis. Clinical study of liver cirrhosis therapy using adipose tissue-derived stromal cells. Autologous adipose tissue-derived stromal/stem (regenerative) cells were administered via intrahepatic arterial transfusion into cirrhotic patients. The obtained adipose tissue-derived stromal cells were shown to contain mesenchymal stem cells.
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