Therapeutic potential of propagated hepatocyte transplantation in liver failure.
Therapeutic potential of propagated hepatocyte transplantation in liver failure.
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DOI：
10.1016/j.jss.2010.12.008
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发表时间：
2011-05
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影响因子：
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通讯作者：
H. Amano;H. Hino;C. Tateno;K. Emoto;Y. Imaoka;C. Yamasaki;T. Itamoto;H. Tashiro;T. Asahara;H. Ohdan;K. Yoshizato
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文献类型：
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作者：
H. Amano;H. Hino;C. Tateno;K. Emoto;Y. Imaoka;C. Yamasaki;T. Itamoto;H. Tashiro;T. Asahara;H. Ohdan;K. Yoshizato
背景本研究旨在评估培养繁殖的同源肝细胞脾内移植对急性肝衰竭（ALF）大鼠的治疗潜力。方法通过完全切除两个前叶（肝脏的 68%）并结扎右叶（肝脏的 24%）蒂，在二肽基肽酶 IV 阴性（DPPIV−）Fischer 344 大鼠中诱导出 SALF。从 DPPIV+Fischer 344 大鼠中分离的肝细胞培养 11 天，增殖 3 倍，所得肝细胞被称为“培养增殖肝细胞 (CPHEP)”。在 ALF 诱导前，将总共 1.5 × 107 个 CPHEP 细胞移植到脾内（CPHEP 组）。同样，移植新鲜分离的肝细胞（FIHEP）作为阳性对照（FIHEP组），注射培养基（CM）作为阴性对照（CM组）。结果CPHEP组的存活时间与FIHEP组相当，且长于CM组（P < 0.01）。 CPHEP和FIHEP移植均改善了血液参数，如氨、总胆红素、谷氨酸丙酮酸转氨酶和谷氨酸草酰乙酸转氨酶；移植还影响肝组织参数，如凋亡率和溴脱氧尿苷标记指数。结论培养增殖的同源肝细胞移植对大鼠 ALF 具有显着的治疗潜力。
BACKGROUNDThis study aimed to evaluate the therapeutic potential of intrasplenic transplantation of culture-propagated homologous hepatocytes in rats suffering from acute liver failure (ALF).METHODSALF was induced in dipeptidyl peptidase IV-negative (DPPIV−) Fischer 344 rats by totally removing the two anterior liver lobes (68% of the liver) and ligating the pedicle of the right lobe (24% of the liver). Hepatocytes isolated from DPPIV+Fischer 344 rats were cultured for 11 d to propagate 3-fold, and the resulting hepatocytes were dubbed “culture-propagated hepatocytes (CPHEPs)”. A total of 1.5 × 107cells of CPHEPs were transplanted intrasplenically before ALF induction (CPHEP group). Similarly, freshly isolated hepatocytes (FIHEPs) were transplanted as a positive control (FIHEP group), and culture medium (CM) was injected into rats as a negative control (CM group).RESULTSThe survival of the CPHEP group was comparable to that of the FIHEP group and longer than that of the CM group (P < 0.01). Both CPHEP and FIHEP transplantation improved blood parameters such as ammonia, total bilirubin, glutamic pyruvic transaminase, and glutamic oxaloacetic transaminase; transplantation also affected liver tissue parameters such as apoptosis rate and bromodeoxyuridine-labeling index.CONCLUSIONSTransplantation of culture-propagated homologous hepatocytes has a remarkable therapeutic potential for ALF in rats.