In vivo hepatic differentiation of mesenchymal stem cells from human umbilical cord blood after transplantation into mice with liver injury

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• 作者：Jiong Yu^a ; ^{yujiong@yahoo.cn} ; Hongcui Cao^a ; ^{caohc70@yahoo.com.cn} ; Jinfeng Yang^a ; ^{jinfengjinfengyang@163.com} ; Qiaoling Pan^a ; ^{zjlspql@126.com} ; Jing Ma^a ; ^{654390166@qq.com} ; Jianzhou Li^a ; ^{lijianzhou1986@163.com} ; Yanyuan Li^b ; ^{liyanyuanhz@yahoo.com.cn} ; Jun Li^a ; ^{lijun918@gmail.com} ; Yingjie Wang^a ; ^{yingjiewang@zju.edu.cn} ; Lanjuan Li^a ; ^{ljli@zju.edu.cn}
• 关键词：Hepatic differentiation ; Mesenchymal stem cells ; Umbilical cord blood ; Transplantation ; Liver injury
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：15 June, 2012
• 卷：422
• 期：4
• 页码：539-545
• 文件大小：1412 K

摘要

Aim

The aim of this study was to analyze the hepatic differentiation potential of human umbilical cord blood-derived mesenchymal stem cells (hUCBMSCs) after transplantation into severe combined immune deficiency (SCID) mice with liver injury induced by D-galactosamine/lipopolysaccharide (GalN/LPS) and to explore the possibility that cells can partially repair GalN/LPS-induced hepatic damage.

Methods

Mononuclear cells (MNCs) were isolated from fresh human umbilical cord blood, characterized by flow cytometry, and then transplanted into GalN/LPS-injured mice. Specimens were collected at 7, 14, 21, and 28 days after hUCBMSC transplantation. Histopathological changes were analyzed by hematoxylin and eosin staining. Polymerase chain reaction (PCR) for a specific marker of human cells, the human Alu sequence, was performed to locate exogenous hUCBMSCs in mouse livers. Expression of human hepatocyte-specific markers such as human albumin (hALB), human alpha-fetoprotein (hAFP), human cytokeratin 18 (hCK18), and human cytokeratin 19 (hCK19) were analyzed by reverse transcriptase (RT)-PCR and immunohistochemical staining.

Results

The hUCBMSCs were positive for the human MSC-specific markers CD271, CD29, CD90, CD105, and CD73, but negative for CD31, CD79b, CD133, CD34, and CD45. Histological findings showed that the hepatic damage in mice was attenuated after hMSC administration, and liver architecture was much better preserved. Human cells in the injured liver of recipient mice were detected by PCR for the human Alu sequence. In addition, expression of markers of hepatic lineage, including hALB, hAFP, hCK18, and hCK19, was detected by immunohistochemistry and RT-PCR in mouse livers after hUCBMSC transplantation, suggesting the formation of hepatocyte-like cells in vivo.

Conclusion

MSCs from hUCB exhibit the potential to differentiate into hepatocyte-like cells in the livers of hUCB-transplanted mice as well as partially repair the liver damage induced by GalN/LPS.