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人脐带间充质干细胞可改善暴发性肝衰竭并提高小鼠存活率。

Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice.

作者信息

Yang Jin-Feng, Cao Hong-Cui, Pan Qiao-Ling, Yu Jiong, Li Jun, Li Lan-Juan

机构信息

The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, 79 Qingchun Road, Hangzhou 310003, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):186-93. doi: 10.1016/s1499-3872(15)60354-x.

DOI:10.1016/s1499-3872(15)60354-x
PMID:25865692
Abstract

BACKGROUND

Cell therapy has been promising for various diseases. We investigated whether transplantation of human umbilical cord mesenchymal stem cells (hUCMSCs) has any therapeutic effects on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced fulminant hepatic failure in mice.

METHODS

hUCMSCs isolated from human umbilical cord were cultured and transplanted via the tail vein into severe combined immune deficiency mice with GalN/LPS-induced fulminant hepatic failure. After transplantation, the localization and differentiation of hUCMSCs in the injured livers were investigated by immunohistochemical and genetic analyses. The recovery of the injured livers was evaluated histologically. The survival rate of experimental animals was analyzed by the Kaplan-Meier method and log-rank test.

RESULTS

hUCMSCs expressed high levels of CD29, CD73, CD13, CD105 and CD90, but did not express CD31, CD79b, CD133, CD34, and CD45. Cultured hUCMSCs displayed adipogenic and osteogenic differentiation potential. Hematoxylin and eosin staining revealed that transplantation of hUCMSCs reduced hepatic necrosis and promoted liver regeneration. Transplantation of hUCMSCs prolonged the survival rate of mice with fulminant hepatic failure. Polymerase chain reaction for human alu sequences showed the presence of human cells in mouse livers. Positive staining for human albumin, human alpha-fetoprotein and human cytokeratin 18 suggested the formation of hUCMSCs-derived hepatocyte-like cells in vivo.

CONCLUSIONS

hUCMSC was a potential candidate for stem cell based therapies. After transplantation, hUCMSCs partially repaired hepatic damage induced by GalN/LPS in mice. hUCMSCs engrafted into the injured liver and differentiated into hepatocyte-like cells.

摘要

背景

细胞疗法对多种疾病具有潜在应用前景。我们研究了人脐带间充质干细胞(hUCMSCs)移植对D - 半乳糖胺/脂多糖(GalN/LPS)诱导的小鼠暴发性肝衰竭是否具有治疗作用。

方法

从人脐带分离出的hUCMSCs进行培养,并通过尾静脉移植到患有GalN/LPS诱导的暴发性肝衰竭的严重联合免疫缺陷小鼠体内。移植后,通过免疫组织化学和基因分析研究hUCMSCs在受损肝脏中的定位和分化情况。通过组织学方法评估受损肝脏的恢复情况。采用Kaplan - Meier法和对数秩检验分析实验动物的存活率。

结果

hUCMSCs高表达CD29、CD73、CD13、CD105和CD90,但不表达CD31、CD79b、CD133、CD34和CD45。培养的hUCMSCs具有成脂和成骨分化潜能。苏木精 - 伊红染色显示,hUCMSCs移植可减少肝坏死并促进肝脏再生。hUCMSCs移植延长了暴发性肝衰竭小鼠的存活率。针对人alu序列的聚合酶链反应显示小鼠肝脏中存在人细胞。人白蛋白、人甲胎蛋白和人细胞角蛋白18的阳性染色表明体内形成了hUCMSCs来源的肝细胞样细胞。

结论

hUCMSC是基于干细胞治疗的潜在候选者。移植后,hUCMSCs可部分修复小鼠体内由GalN/LPS诱导的肝损伤。hUCMSCs植入受损肝脏并分化为肝细胞样细胞。

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