[1]	王海莹, 吕 冰, 李 辉, 王顺义. 减压植骨融合内固定治疗退变性腰椎滑脱：基于脊柱骨盆参数预测患者的功能预后[J]. 中国组织工程研究, 2021, 25(9): 1393-1397.
[2]	刘 钊, 徐西林, 申意伟, 张晓峰, 吕 航, 赵 军, 王政春, 刘旭卓, 王海涛. 塌陷预测方法联合分期分型对股骨头坏死治疗的指导作用与前景[J]. 中国组织工程研究, 2021, 25(6): 929-934.
[3]	柳 扬, 龚 毅, 范 伟. 构建靶向型Pluronic F127/芒柄花黄素纳米复合体系体外抗肝癌活性[J]. 中国组织工程研究, 2021, 25(4): 526-531.
[4]	梁美富, 曲淑华. 依据反向传播神经网络建模预测骨骼肌的最佳功率负荷[J]. 中国组织工程研究, 2021, 25(23): 3641-3647.
[5]	陈 晓, 郭 智, 陈丽娜, 刘玄勇, 张弋慧智, 李旭绵, 王月乔, 韦丽娅, 谢 晶, 蔺 莉. 自体外周血造血干细胞动员采集的影响因素[J]. 中国组织工程研究, 2021, 25(19): 2958-2962.
[6]	覃艳春, 荣 震, 蒋锐沅, 付 彬, 洪晓华, 莫春梅. 中药复方制剂抑制CD133+肝癌干细胞增殖及干性转录因子的表达[J]. 中国组织工程研究, 2021, 25(19): 3016-3023.
[7]	孙维兴, 赵永超, 赵然尊 . 间充质干细胞移植治疗心肌梗死：问题、症结及新突破[J]. 中国组织工程研究, 2021, 25(19): 3103-3109.
[8]	沈 浮, 邝高艳, 杨 卓, 文 猛, 朱恺民, 余桂枝, 徐无忌, 邓 博. 类风湿关节炎差异表达基因的免疫浸润机制及潜在中药治疗预测[J]. 中国组织工程研究, 2021, 25(14): 2183-2191.
[9]	曹琳琳, 丁凯阳, 宋 浩, 吴国林, 胡茂贵, 范丹丹, 周晨阳, 王翠翠, 封媛媛. 自体造血干细胞移植治疗恶性淋巴瘤的疗效及影响因素[J]. 中国组织工程研究, 2021, 25(13): 1993-1998.
[10]	张文坚, 马灵甫, 王志敏, 莫文健, 周睿卿. 异基因造血干细胞移植患者的四肢肌肉量及影响因素调查[J]. 中国组织工程研究, 2021, 25(13): 1999-2004.
[11]	岑妍慧, 夏 猛, 贾 微, 罗伟生, 林 江, 陈松林, 陈 炜, 刘 鹏, 黎明星, 李景云, 李曼莉, 艾丁丁, 蒋云霞. 黄芩素能下调诱捕受体3表达抑制肝癌干细胞的生物学行为[J]. 中国组织工程研究, 2020, 24(7): 1023-1029.
[12]	张素平, 孙 玲, 万鼎铭, 曹伟杰, 李 丽, 刘长凤, 刘玉峰, 王 叨, 郭 荣, 姜中兴, 谢新生. 非血缘外周血造血干细胞移植治疗重型再生障碍性贫血的有效性[J]. 中国组织工程研究, 2020, 24(31): 4994-5001.
[13]	刘晓银, 钟 琳, 郑 博, 魏 攀, 代 晨, 胡良聪, 王甜甜, 梁小龙, 张 赛, 王晓丽. 弥散张量成像预测3D打印支架促进脊髓损伤后运动功能恢复[J]. 中国组织工程研究, 2020, 24(28): 4547-4554.
[14]	冯 源, 韩志琪, 周 诺. 内皮祖细胞促进血管发生及新骨生成辅助治疗骨缺损 [J]. 中国组织工程研究, 2020, 24(25): 4046-4053.
[15]	闫 延, 程崇杰, 张启栋, 王卫国, 郭万首. 骨科手术相关创伤后应激障碍的发生及高危因素分析[J]. 中国组织工程研究, 2020, 24(24): 3897-3903.

End-stage liver cirrhosis has a high incidence rate in China and threatens human’s life, but there have been no practical and effective measures.
Recently, bone marrow-derived stem cells differentiation into hepatocytes has been well studied. Transplantation of stem cells, which has been applied in various medical fields, provides new ideas for treatment of decompensated cirrhosis[1]. However, it remains controversy as to whether there is a correlation between stem cells transplantation and liver cancer occurrence after intrahepatic microenvironment alters in liver cirrhosis[2].
In addition to alpha-fetoprotein (AFP), a widely accepted marker of liver cancer, AFP variants (AFP-L3) has been also considered an important predictor of diagnosis of liver cancer[3].
To investigate whether AFP-L3 can be used as a predicative index for treatment of liver cancer using stem cells transplantation, the present study monitored the serum levels of AFP and AFP-L3 in 44 decompensated cirrhosis patients who underwent transplantation of peripheral blood stem cells prior to and after surgery and analyzed the relationship between stem cells transplantation for treatment of decompensated cirrhosis and the malignant phenotype of liver cancer, so as to assess the safety of this treatment method.

Transplantation of autologous stem cells for treatment of liver cirrhosis has been widely reported. But up to now, there exist some concerns for clinical physicians, including relationship between stem cells and post-transplantation prognosis/turnover of liver cirrhosis, directed differentiation of stem cells in the impaired liver, and malignant phenotype[9]. It is extremely important to early detect and periodically monitor the predictor of liver cirrhosis transformation into liver cancer. AFP is the most specific index of primary liver cancer[10], but increased AFP concentration is also observed in some patients with liver cirrhosis or chronic liver disease. At present, AFP > 400 µg/L for successive 8 weeks is selected as a criterion of diagnosis of hepatocellular liver cancer by the majority of hospitals[11]. A dynamic observation of AFP concentration change is necessary for patients showing successive low-concentration AFP. Therefore, it is difficult to distinguish the benign and malignant lesions only according to AFP results. Thus, it is of clinical significance to detect AFP variants, in particular for patients showing 20-400 µg/LAFP. Evidence exists that AFP-L3 ≥10% shows a sensitivity of 91.1% in diagnosis of liver cancer and a specificity of 92.9% in diagnosis of chronic liver disease[12]. Patients with hepatocellular liver cancer show greater AFP-L3 mean value and AFP-L3-positive rate than patients with liver cirrhosis and chronic hepatitis. Therefore, detection of AFP-L3 helps distinguish patients with and without hepatocellular liver cancer. In particular in patients showing AFP < 400 µg/L, AFP-L3 (%)≥10% is a good differential diagnosis index to distinguish the benigh liver disease from malignant ones. Therefore, it is of important clinical value to detect AFP-L3 in low-concentration AFP samples[13].
Liver cirrhosis tubercle is often detected in liver cirrhosis patients through imaging examination. If increased AFP concentration is accompanied, it is potential for liver cancer. AFP-L3 can be used to distinguish liver cirrhosis tubercle and space-occupying lesion due to liver cancer. Moreover, AFP-L3 selected as a diagnosis index of liver cirrhosis is not limited by AFP > 400 µg/L which serves a diagnosis criterion of liver cancer. AFP-L3 >10% demonstrates increased malignant hepatocytes, indicating a great possibility of liver canceration. Following carcinectomy, the 5-year and 10-year survival rate are 64.8% and 46.3%, respectively, for patients with liver cancer presenting cancerous tubercle < 5 cm considered stage I liver cancer, while they were 37.1% and 29.2%, respectively, for patients presenting with cancerous tubercle > 5 cm; following carcinectomy, patients with smaller sized tumor would acquire better therapeutic effects[14]. Therefore, early diagnosis of liver cancer is very important for the therapeutic effects of hepatocellular liver cancer. Table 2 shows that there was no significant difference in AFL-L3-positive rate among patients with different AFP concentrations, indicating that AFP-L3-positive rate is not influenced by change of AFP concentration. Therefore, it is helpful to detect AFP-L3 in serum for identification of malignant liver diseases, in particular for early diagnosis of small-sized liver cancer and differential diagnosis of low-concentration AFP liver disease. 
The 44 patients undergoing stem cells transplantation for treatment of liver cirrhosis included in this study are all liver cirrhosis patients, as diagnosed by color doppler flow imaging. When discharge, the clinical diagnosis of hepatocellular liver cancer was not made, but AFP and AFP-L3 were periodically followed up and AFP-L3 > 10% was taken as a positive criterion of liver cancer. Results demonstrated that during a 6-month follow-up period, five patients were lost, and 39 patients could provide complete data; no liver cancer tubercle was found in patients with AFP at critical value and AFP-L3 positive expression at 6 months after discharge, as shown by B ultrasonic and CT imaging examinations. Studies demonstrated that AFP-L3 positive expression could be detected 6-12 months after imaging exanimation[15-16]. The majority of liver cirrhosis patients with increased AFP-L3 are diagnosed suffering from hepatocellular liver cancer within 3-18 months. Detection of AFP-L3 could predict the occurrence of liver cancer when characteristic space-occupying lesions have not been detected through imaging examination. It is necessary to follow up and closely monitor the patients with AFP-L3 > 10%. The relationship between stem cells transplantation and liver cancer has not been fully elucidated owing to small sample size. In addition, transplantation pathway would influence the process of intrahepatic retention, growth, and differentiation of stem cells. Although stem cells transplanted via peripheral vein can reach the liver, but only a few stem cells are included in intrahepatic directed differentiation after systemic circulation[17]. To enhance the amount of stem cells transplanted in the intrahepatic directed differentiation, transhepatic arterial transplantation is widely applied in China. Transhepatic arterial transplantation does not favor implantation of stem cells owing to fast arterial blood flow and thin inner diameter although it is simple and convenient to operate[17]. Wu et al[18] performed intrahepatic transplantation of stem cells via portal vein and detected isolated stem cells in portal venous ramuli and central vein of the liver sample ex vivo at 12 days after transplantation. Stem cells transplanted via this pathway can be integrated into recipient’s hepatic plate and differentiate into mature hepatocytes[18].
Results from this study demonstrated that at 2 months after surgery, serum level of AFP showed a transient increase in 11 patients, but AFP-L3 was not greatly changed, indicating that AFP-L3 index does not change markedly in the inflammatory lesions, which is accordance with the specificity of tumor marker.
Preliminary clinical results from this study demonstrated that clinical symptoms and hepatic function of decompensated cirrhosis patients recovered to some extent following intrahepatic transplantation of peripheral blood stem cells via portal vein. Detection results of AFP-L3, a serological marker of liver cancer, did not demonstrate the presence of malignant biological phenotype within short time period, but because follow-up time is very short, the relationship between stem cells transplantation and intrahepatic microenvironment, intrahepatic malignant biological phenotype cannot be fully explained and the therapeutic effects and safety require further investigation.

	阅读次数
	全文
	摘要