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使用脂肪来源干细胞对小鼠慢性肝损伤进行细胞治疗

Cell Therapy Using Adipose-Derived Stem Cells for Chronic Liver Injury in Mice.

作者信息

Ohashi Kazuo, Matsubara Yoshinori, Tatsumi Kohei, Kohori Ayako, Utoh Rie, Kakidachi Hiroshi, Horii Akihiro, Tsutsumi Masahiro, Okano Teruo

机构信息

Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University , Shinjuku, Tokyo , Japan.

† Corporate R&D Center, Olympus Corporation , Hachioji, Tokyo , Japan.

出版信息

Cell Med. 2012 May 14;3(1-3):113-119. doi: 10.3727/215517912912X639432. eCollection 2012 Jan.

Abstract

The present study investigated whether transplantation of autologous adipose-derived stem cells (ASCs) administered into the systemic circulation of a mouse with chronic liver injury provides therapeutic efficacy in the absence of any undesirable side effects. The ASCs used were isolated from mice with the same genetic background as the recipient mice and expanded in vitro. For the induction of chronic liver injury, mice were repetitively administered twice a week with CCl, a well-known hepatotoxin, for a period of 4 weeks. One day after the eighth dose of CCl, ASC transplantation was performed by tail vein injection and subsequently followed by two additional doses of CCl administration. The recipient mice were divided into four groups (vehicle control, 1.5×10, 1.5×10, and 1.5×10 ASCs per mouse). One day after the final CCl administration, all mice were sacrificed to assess serum markers and liver histology. The level of serum markers for liver injury and hepatic function did not differ among the four groups. Similarly, no difference was observed in the liver histology between groups. Cell transplantation with ASCs in our model of chronic liver failure did not result in any observable side effects, but from our results, a single application of ASCs seems to be ineffective in improving liver injury.

摘要

本研究调查了将自体脂肪来源干细胞(ASC)移植到慢性肝损伤小鼠的体循环中是否能在无任何不良副作用的情况下产生治疗效果。所用的ASC是从与受体小鼠具有相同遗传背景的小鼠中分离出来并在体外进行扩增的。为诱导慢性肝损伤,小鼠每周两次重复给予著名的肝毒素CCl,持续4周。在第八次给予CCl一天后,通过尾静脉注射进行ASC移植,随后再额外给予两次CCl。将受体小鼠分为四组(载体对照组、每只小鼠1.5×10、1.5×10和1.5×10个ASC)。在最后一次给予CCl一天后,处死所有小鼠以评估血清标志物和肝脏组织学。四组之间肝损伤和肝功能的血清标志物水平没有差异。同样,各组之间在肝脏组织学方面也未观察到差异。在我们的慢性肝衰竭模型中,用ASC进行细胞移植未产生任何可观察到的副作用,但从我们的结果来看,单次应用ASC似乎对改善肝损伤无效。

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