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人脂肪组织来源的干细胞促进毒损伤大鼠模型的肝再生。

Human adipose tissue derived stem cells promote liver regeneration in a rat model of toxic injury.

机构信息

Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine, Heidelberg University Hospital-Ethianum, Voßstraße 6, 69115 Heidelberg, Germany.

出版信息

Stem Cells Int. 2013;2013:534263. doi: 10.1155/2013/534263. Epub 2013 Nov 7.

Abstract

In the light of the persisting lack of donor organs and the risks of allotransplantations, the possibility of liver regeneration with autologous stem cells from adipose tissue (ADSC) is an intriguing alternative. Using a model of a toxic liver damage in Sprague Dawley rats, generated by repetitive intraperitoneal application of retrorsine and allyl alcohol, the ability of human ADSC to support the restoration of liver function was investigated. A two-thirds hepatectomy was performed, and human ADSC were injected into one remaining liver lobe in group 1 (n = 20). Injection of cell culture medium performed in group 2 (n = 20) served as control. Cyclosporine was applied to achieve immunotolerance. Blood samples were drawn weekly after surgery to determine liver-correlated blood values. Six and twelve weeks after surgery, animals were sacrificed and histological sections were analyzed. ADSC significantly raised postoperative albumin (P < 0.017), total protein (P < 0.031), glutamic oxaloacetic transaminase (P < 0.001), and lactate dehydrogenase (P < 0.04) levels compared to injection of cell culture medium alone. Transplanted cells could be found up to twelve weeks after surgery in histological sections. This study points towards ADSC being a promising alternative to hepatocyte or liver organ transplantation in patients with severe liver failure.

摘要

鉴于供体器官的持续缺乏和同种异体移植的风险,利用自体脂肪组织(ADSC)中的干细胞进行肝脏再生的可能性是一种引人注目的替代方法。本研究采用反复腹腔内给予反式视黄酸和顺丁烯二酸单乙酯诱导的 Sprague Dawley 大鼠肝毒性损伤模型,研究了人 ADSC 支持肝功能恢复的能力。进行 2/3 肝切除术,将人 ADSC 注射到第一组(n = 20)的一个剩余肝叶中。第二组(n = 20)注射细胞培养液作为对照。应用环孢素实现免疫耐受。术后每周抽取血样以测定与肝脏相关的血液值。术后 6 周和 12 周时处死动物并分析组织学切片。与单独注射细胞培养液相比,ADSC 显著提高了术后白蛋白(P < 0.017)、总蛋白(P < 0.031)、谷草转氨酶(P < 0.001)和乳酸脱氢酶(P < 0.04)水平。移植细胞在术后 12 周的组织学切片中仍可找到。这项研究表明,ADSC 可能是严重肝功能衰竭患者肝细 胞或肝器官移植的一种有前途的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f39e/3839126/17fdfa39987a/SCI2013-534263.001.jpg

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