心肌内环境对骨髓干细胞转化成心肌细胞的影响的研究

The influence of myocardial microenvironment on defferentiation of bone marrow stem cells into myocardial cells

目的 探讨心肌内环境对骨髓基质干细胞 (MSCs )向心肌细胞转化的影响。方法 利用梯度离心法分离大鼠MSCs;然后将MSCs分别移植到正常和疤痕心肌组织中 ,在 10d和 2 0d时观察移植细胞的情况。结果 移植的细胞在正常心肌组织中存活并向心肌细胞转化。HE染色结果 :胞浆嗜酸性 ,胞核居细胞中央 ,免疫组化染色鉴定BrdU阳性 ;心肌特异性抗体 (肌钙蛋白和肌凝蛋白重链 )结果呈阳性。在疤痕心肌组织中未见骨髓基质干细胞向心肌细胞的转化。结论 正常的心肌组织内环境能促进干细胞向心肌细胞转化 ,在疤痕组织中不能实现骨髓干细胞向心肌细胞的转化 ,因此 ,利用骨髓干细胞进行细胞移植时 ,要根据不同的治疗方法和目的 ,选取不同状态 (诱导否 )的干细胞。

Objective To study the influence of myocardial microenvironment on the defferentiation of BMCs into myocardial cells.Methods MSCs were isolated from isogenic SD rats,culture expanded.The MSCs were then labelled with bromodeoxyuridine(Brdu).The MSCs were injected into the myocardial tissue of normal rates and the myocardial scar of three weeks after myocardial infarction created by coronary artery ligation.The hearts were harvested 10 to 20 days later and stained immunohistochemically for phenotypic markers and stained for histologieal studies.Results The MSCs in normal myocardial tissue appeared to be morphologically distinct from the MSCs in the scar tissue.The MSCs in normal myocardial tissue appeared more myotube-like with elongated nuclei lin-early alligned with one another,and stained positive for the cardiomyocyte specific marker-- troponin I and myocin heavy chain.The MSCs in the scar tissue in contrast disappear and we could see that transplanted BMCs necrosed and disappeared and a lot of lymphocytes and fibroblasts and capillaries in the transplanted scar tissues.Other cells drived from BMCs were not seen.We found also that control scar tissues were homogenous in appearances and did not contain any like-cardiomyocytes converted from BMCs.Conclusion Myocardial microenvironment affect the defferentiation of BMCs into myocardial cells.Unmodified MSCs may induce to differentiate into cardiomyocyte phenotype in normal myocardial tissues.Whereas converting scar into myogenic tissue,should be facilitated by preprogramming of MSCs before implantation.