中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (6): 1064-1067.doi: 10.3969/j.issn.1673-8225.2010.06.023

• 干细胞移植 • 上一篇    下一篇

静脉移植骨髓间充质干细胞联合重组人生长激素对充血性心肌病大鼠心肌和血管组织的修复

姚 巍1，王凤芝2   

  1. 山西医科大学第二医院干六楼，   1心血管科，2心内科，山西省太原市 030001
  • 出版日期:2010-02-05 发布日期:2010-02-05
  • 作者简介:姚 巍，男，1968年生，辽宁省沈阳市人，汉族，山西医科大学在读博士，副教授，主要从事心血管内科诊治和干细胞方面的研究。 yaowei36@sohu.com
  • 基金资助:

    山西省高校科研开发项目（200811073）；山西医科大学博士科题。

Intravenous transplantation of bone marrow mesenchymal stem cells in combination with recombinant human growth hormone repairs myocardium and vascular tissues in rats with congestive cardiomyopathy

Yao Wei1, Wang Feng-zhi2   

  1. 1Cardiovascular Department, 2Department of Cardiology, Sixth Floor of Second Hospital, Shanxi Medical University, Taiyuan   030001, Shanxi Province, China
  • Online:2010-02-05 Published:2010-02-05
  • About author:Yao Wei, Studying for doctorate, Associate professor, Cardiovascular Department, Sixth Floor of Second Hospital, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China yaowei36@sohu.com
  • Supported by:

    the Science Research and Development Program of Higher Learning School of Shanxi Province, No.200811073*;
    the Doctoral Subject of Shanxi Medical University*

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495

被引次数

2

摘要：

背景：骨髓间充质干细胞静脉移植后，能否归巢至心脏受损部位和分化为心肌样细胞尚无统一定论。

目的：探讨重组人生长激素联合骨髓间充质干细胞静脉移植对充血性心肌病大鼠心肌和血管新生的影响。

方法：密度梯度离心和贴壁筛选法获得大鼠骨髓间充质干细胞。模型组、细胞移植组、生长激素组、联合组大鼠均在阿霉素诱导下建立心脏衰竭模型。造模后，细胞移植组经静脉注入BrdU标记的骨髓间充质干细胞8×1013 L-1；生长激素组皮下注射重组人生长激素2 U/(kg·d)，连续14 d；联合组行骨髓间充质干细胞移植与重组人生长激素注射。4周后取材，BrdU+MHC及BrdU+Actin免疫组化染色确定骨髓间充质干细胞的归巢情况，评价移植细胞向心肌样细胞和血管内皮细胞的分化，苏木精-伊红染色检测血管密度。

结果与结论：与细胞移植组比较，联合组BrdU免疫组化阳性率显著升高(P < 0.001)；BrdU+MHC双染和BrdU+Actin双染后心肌样细胞、血管内皮细胞均显著增多(P < 0.001)。与模型组比较，生长激素组、细胞移植组、联合组的总血管密度、微血管密度、毛细血管密度均显著升高(P < 0.001)，后3组间比较无明显差异(P > 0.05)。结果证实骨髓间充质干细胞静脉移植后可归巢到心脏，对充血性心肌病大鼠心肌和血管有明显修复作用，能在损伤处区存活、生长，并向心肌样细胞、血管内皮细胞方向分化，增加损伤处血管密度；生长激素可以改善微环境，加强骨髓间充质干细胞向心肌样细胞、血管内皮细胞的转化率。

关键词: 阿霉素, 心力衰竭, 重组人生长激素, 静脉移植, 骨髓间充质干细胞

Abstract:

BACKGROUND: It is controversial whether bone marrow mesenchymal stem cells can retain in cardiac injured position, or differentiate into cardiomyocytes or not.

OBJECTIVE: To study the effects of recombinant human growth hormone and bone marrow mesenchymal stem cells (BMSCs) intravenous transplantation on myocardium and angiogenesis in rats with congestive cardiomyopathy.

METHODS: BMSCs were collected from rats by density gradient centrifugation and adhesive-screening method. Models of cardiac failure were established using adriamycin induction in the model, cell transplantation, growth hormone and combination groups. Following model establishment, cell transplantation group received BrdU-labeled BMSCs (8×1013/L) via vein. Growth hormone group underwent subcutaneous injection of human growth hormone 2 U/kg per day, for 14 consecutive days. Combination group received injection of human growth hormone and BMSC transplantation. At week 4, samples were collected. Immunohistochemical staining for BrdU+MHC and BrdU+Actin was used to determine homing of BMSCs to evaluate the differentiation of transplanted cells into cardiomyocytes and vascular endothelia cells. Hematoxylin-eosin staining was utilized to detect vascular density.

RESULTS AND CONCLUSION: Compared with the cell transplantation group, positive rate of Brdu immunohistochemistry was increased in the combination group (P < 0.001). The number of cardiomyocytes and vascular endothelia cells was significantly increased following Brdu+MHC and Brdu+Actin staining (P < 0.001). Compared with the model group, total vascular density, microvessel density and capillary density were significantly increased in the growth hormone, cell transplantation and combination groups (P < 0.001). No significant difference was determined among growth hormone, cell transplantation and combination groups (P > 0.05). Intravenous transplantation of BMSCs could repair cardiomyocytes and vascular endothelial cells by homing into the heart. BMSCs could survive in damaged area and differentiate into cardiomyocytes or vascular endothelial cells and increase the vascular density significantly. Growth hormone could improve microenvironment and raise rates of differentiating into cardiomyocytes or vascular endothelial cells.

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