自体骨髓间叶干细胞诱导分化移植重建窦房结起搏功能的实验研究

Cardiac Biological Autonomic Pacemaker Restored by Autologous Transplantation and Committed Differentiation of Bone Marrow Mesenchymal Stem Cells

目的 :探索应用骨髓干细胞治疗病态窦房结综合征的生物介入方法。 方法 :选取犬 6只 ,随机分为实验组和对照组 ,每组 3只。抽取犬自体骨髓 ,分离培养扩增骨髓间叶干细胞 ,并在体外应用 5 氮胞苷进行诱导分化。应用射频技术损伤犬窦房结 ,建立动物病态窦房结综合征模型。将溴脱氧尿嘧啶核苷 (BrdU)标记的且诱导分化的骨髓间叶干细胞自体移植到窦房结区 ,应用心电图、组织病理、免疫组化等技术观察干细胞移植治疗效果。 结果 :在动物病态窦房结综合征模型 ,自体移植骨髓干细胞后 ,心电图示窦房结功能明显改善 ;病理与免疫组化示移植的骨髓干细胞在窦房结区分化为拟窦房结细胞与血管内皮细胞 ,并与宿主细胞建立缝隙连接。 结论 :自体移植诱导分化的骨髓间叶干细胞可改善窦房结自律起搏功能。

Objective: To restore cardiac autonomic pace function by autologous transplantation and committed differentiation of bone marrow mesenchymal stem cells, and explore the technique for the treatment of sick sinus syndrome. Methods: Mesenchymal stem cells isolated from canine bone marrow were culture expanded and differentiated in vitro by 5 azacytidine. The models of sick sinus syndrome in canines were established by ablating sinus node with radio frequency technique. Differentiated mesenchymal stem cells labeled by BrdU were autologous transplantated into sinus node area through direct injection. The effects of autologous transplantation of mesenchymal stem cells on cardiac autonomic pace function in sick sinus syndrome models were evaluated by electrocardiography, pathologic and immunohistochemical staining technique. Results: There was distinct improvement on pace function of sick sinus syndrome animal models while differentiated mesenchymal stem cells were auto transplanted into sinus node area. Mesenchymal stem cells transplanted in sinus node area were differentiated into similar sinus node cells and endothelial cells in vivo, and established gap junction with native cardiomyocytes. Conclusion: The committed induced mesenchymal stem cells transplanted into sinus node area can be differentiated into analogous sinus node cells and improve pace function in canine sick sinus syndrome models.