A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells.

A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells.
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DOI:
10.1002/hep4.1071
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发表时间:
2017-09
影响因子:
5.1
通讯作者:
Sakaida I
Sakaida I
中科院分区:
医学2区
文献类型:
--
作者:
Matsuda T;Takami T;Sasaki R;Nishimura T;Aibe Y;Paredes BD;Quintanilha LF;Matsumoto T;Ishikawa T;Yamamoto N;Tani K;Terai S;Taura Y;Sakaida I

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我们一直在开发一种使用培养的自体骨髓间充质干细胞(BMSCs)治疗肝硬化的方法。在考虑进行人体临床试验之前,必须确认BMSC输注在中型至大型动物中的安全性和有效性;因此,我们开发了犬肝纤维化模型。从犬肱骨中抽取少量骨髓液,以评估BMSCs的特性。我们在每只犬的胃中植入静脉导管,并在颈后植入皮下输液港。通过导管重复注射CCl 4以诱导肝硬化。CCl_4注射10周后,将8只犬随机分为两组:不输注细胞组(对照组)和经外周静脉输注自体BMSC组(BMSC组)。在输注前和输注后4周进行各种测定。在BMSC输注后4周,BMSC组中天狼星红染色的肝纤维化面积显著减少,与吲哚菁绿色半衰期显著缩短和肝功能改善一致。结论:我们建立了一个有用的犬肝纤维化模型,并证实了培养的自体BMSC输注改善肝纤维化而无副作用。(Hepatology Communications 2017;1:691-703)
We have been developing a therapy for liver cirrhosis using cultured autologous bone marrow–derived mesenchymal stem cells (BMSCs). Before human clinical trials can be considered, the safety and efficacy of BMSC infusion in medium to large animals must be confirmed; thus, we developed a canine liver fibrosis model. A small amount of bone marrow fluid was aspirated from the canine humerus to assess the characteristics of BMSCs. We implanted a venous catheter in the stomach and a subcutaneous infusion port in the back of the neck of each canine. Repeated injection of CCl4 through the catheter was performed to induce liver cirrhosis. After 10 weeks of CCl4 injection, eight canines were equally divided into two groups: no cell infusion (control group) and autologous BMSC infusion through the peripheral vein (BMSC group). A variety of assays were carried out before and 4 weeks after the infusion. The area of liver fibrosis stained with sirius red was significantly reduced in the BMSC group 4 weeks after BMSC infusion, consistent with a significantly shortened half‐life of indocyanine green and improved liver function. Conclusion: We established a useful canine liver fibrosis model and confirmed that cultured autologous BMSC infusion improved liver fibrosis without adverse effects. (Hepatology Communications 2017;1:691–703)
DOI: 10.1111/vru.12059
发表时间: 2013-11-01
期刊: Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association
影响因子: --
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影响因子: 4.2
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发表时间: 2013-12-01
影响因子: 6.4
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