骨髓间充质干细胞移植在肝纤维化治疗中的应用

吕素莉; 马勇; 丁体龙

骨髓间充质干细胞移植在肝纤维化治疗中的应用

1. 蚌埠医学院医学检验系
2. 解放军第123医院南京军区肝病中心

基金项目:

南京军区医学科技创新经费资助重点课题(11Z012)；

详细信息

中图分类号: R575.2
计量
- 文章访问数: 2964
- HTML全文浏览量: 21
- PDF下载量: 683
- 被引次数: 0
出版历程
- 出版日期: 2012-11-20

Bone marrow mesenchymal stem cells as therapy for hepatic fibrosis

Research funding:

摘要

摘要:
目的探讨大鼠骨髓间充质干细胞(BMSC)对肝纤维化大鼠模型的治疗效果,为临床自体BMSC移植治疗肝脏疾病提供实验基础和理论依据。方法四氯化碳(CCl4)腹腔注射构建SD大鼠肝纤维化模型。以绿色荧光蛋白(GFP)标记的正常SD大鼠BMSC为细胞来源,于造模后第10周经尾静脉植入模型鼠体内,对照组同法注入生理盐水。4周后取大鼠肝脏进行病理学检测,同时采集大鼠血液,检测血清肝纤维化指标和肝功能指标。结果 (1)成功构建SD大鼠肝纤维化模型。(2)体外分离获得了高纯度贴壁生长的大鼠BMSC,并用携带GFP报告基因的慢病毒成功对其进行感染,感染率达80%以上。(3)经BMSC移植的大鼠肝脏中可检测到GFP阳性的细胞,主要沿着中央静脉及汇管区周围纤维间隔分布。免疫组织化学结果显示GFP阳性细胞呈肝样细胞形态,且与肝组织相容。(4)BMSC移植组与模型对照组和生理盐水组相比,病理检测肝纤维化程度减轻,血清学指标好转。结论BMSC移植能抑制大鼠肝纤维化发展,部分逆转肝纤维化进程,有效改善肝脏功能,为临床自体BMSC移植治疗肝脏疾病提供实验基础。
- 肝硬化 /
- 干细胞移植 /
- 骨髓细胞 /
- 间质干细胞
Abstract:
Objective To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSC) in a rat model of liver fibrosis, so as to provide an experimental foundation and theoretical basis for the clinical treatment of human hepatic disease by transplantation of autologous BMSC.Methods Carbon tetrachloride (CCl4) was injected intraperitoneally to induce rat liver fibrosis.BMSC were harvested from uninduced, healthy rats, infected with lentivirus expressing green fluorescent protein (GFP) , and transplanted into the fibrosis-induced rat via tail vein injection at week 10 after model establishment.A negative control group was injected with saline.Four weeks later, the livers were excised for pathologic examination and the venous blood was collected to test the serological fibrosis parameters and indices of liver function.Results The rat model of liver fibrosis was successfully established.More than 80% of the isolated BMSC were successfully infected with the GFP lentiviral vector.After transplantation, GFP-positive cells were detected in the livers of recipient rats, with the majority being distributed along the fibrous septa around the central vein and portal area.In addition, the GFP-positive cells showed a hepatocyte-like structure and were compatible with hepatic tissue.The rats treated with BMSC had appreciably less hepatic fibrosis and better serological indices than the untreated model group.Conclusion BMSC transplantation can inhibit the progression of liver fibrosis and possibly restore liver function in a rat model.
- liver cirrhosis /
- stem cell transplantation /
- bone marrow cells /
- mesenchymal stem cells

HTML全文

参考文献(17)

[1]Conget PA, Minguell JJ.Phenotypical and functional properties ofhuman bone marrow mesenchymal progenitor cells[J].J Cell Phys-iol, 1999, 181 (1) :67-73.

[2]Oqura Y, Hamanoue M, Tanabe G, et al.Hepatocyte growth factorpromotes liver regeneration and protein synthesis after hepatectomy incirrhotic rats[J].Hepatogastroenterology, 2001, 48 (38) :545-549.

[3]Tuan RS, Boland G, Tuli R.Adult mesenchymal stell cells and cell-based tissue engineering[J].Arthritis Res Ther, 2003, 5 (1) :32-45.

[4]王彤, 符岳, 方向韶, 等.体外诱导骨髓间充质干细胞向心肌细胞的分化和鉴定[J].中山大学学报 (医学科学版) , 2007, 28 (Suppl 3) :9-11.

[5]Schwartz RE, Reyes M, Koodie L, et al.Multipotent adult progeni-tor cells from bone marrow differentiate into function hepatocyte-like cells[J].J Clin Invest, 2002, 109 (10) :1291-1302

[6]Colter DC, Class R, Digirolamo CM, et al.Rapid expansion of re-cycling stem cells in cultures of plastic2adherent cells from humanbone marrow[J].Proc Natl Acad Sci USA, 2000, 97 (7) :3213-3218.

[7]Harting MT, Jimenez F, Cox CS.Isolation of mesenchymal stemcells (MSC) from green fluorescent protein positive (GFP+) trans-genic rodents:The grass is not always green (er) [J].Stem CellsDev, 2008.[Epub ahead of print].

[8]罗衍波, 陈斌, 倪勇, 等.慢病毒转染大鼠骨髓间充质干细胞研究[J].中国热带医学, 2009, 9 (2) :235-236.

[9]陈慧玲, 白海.慢病毒载体转染人骨髓间充质干细胞后其分化潜能的研究[J].中国实验血液学杂志, 2009, 17 (2) :400-403.

[10]赵科研, 王辉山, 候明晓, 等.不同数目骨髓间充质干细胞移植对大鼠肺损伤的抑制作用[J].中国比较医学杂志, 2012, 22 (1) :34-38.

[11]Sordi V.Mesenchymal stell cell homing capacity[J].Transplanta-tion, 2009, 87 (Suppl 9) :s42-s45.

[12]Karp JM, Leng Teo GS.Mesenchymal stell cell homing:the devil isin the details[J].Cell Stem Cell, 2009, 4 (3) :206-216.

[13]Wang T, Tang W, Sun S, et al.Intravenous infusion of bone mar-row mesenchymal stem cells improves myocardial function in a ratmodel of myocardial ischemia[J].Crit Care Med, 2007, 35 (11) :2587-2593.

[14]Ries C, Egea V, Karow M, et al.MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of humanmesenchymal stemcells:differential regulation by inflammatory cytokines[J].Blood, 2007, 109 (9) :4055-406.

[15]Neuss S, Schneider RK, Tietze L, et al.Secretion of fibrinolytic en-zymes facilitates humanmesenchymal stem cell invasion into fibrinclots[J].Cells Tissues Organs, 2010, 191 (1) :36-46.

[16]Sakaida I, Terai S, Yamamoto N, et al.Transplantation of bone mar-row cells reduces CCl4-induced liver fibrosis in mice[J].Hepatology, 2004, 40 (6) :1304-1311.

[17]DiBonzo LV, Ferrero I, Cravanzola C, et al.Human mesenchymal stemcells as a two-edged sword in hepatic regenerativemedicine:engraft-ment and hepatocyte differentiation versus profibrogenic po-tential[J].Gut, 2008, 57 (2) :223-231.

施引文献

资源附件(0)

访问统计