骨髓干细胞植入正常或慢性梗死心肌后短期内移植细胞的分布及可利用度

目的采用心肌内注射方法将骨髓间充质干细胞(BMSCs)植入到正常或慢性梗死心肌中后, 研究短期内植入细胞的分布和可利用度。方法采用选择性冠状动脉结扎方法建立大鼠慢性心肌梗死模型( n =9) 。1个月后, 采用心肌内注射方法将 111 铟 - 羟基喹啉 ( 111Indium- oxine, 111In) 同位素标记的自体 BMSCs (2×106/50μL)植入到慢性梗死心肌和正常对照心肌中( n =6) 。采用序列平面针孔闪烁扫描方法测定 BMSCs移植后 2 h、1 d、3 d、7 d 时的心肌 111In 的放射活性, 并计算植入细胞在心肌内的驻留率。于细胞移植术后第 7 天切取制备心脏横断面冷冻切片, 进行组织放射微成像(Micro- imaging)和组织病理学分析, 观察植入细胞在心肌内的分布情况。结果慢性心肌梗死(MI)组的心肌 111In 的放射活性在所有测定的时间点均显著高于正常对照组(P<0.01)。心肌放射强度实测值在经由各相应时间点 BMSCs细胞 111In 的自发泄漏率的体外标定值校正后, 计算得出植入的 BMSCs 细胞在慢性梗死心肌(MI 组)中的驻留率平均为 60%, 而在正常对照组心肌中细胞的驻留率只有 25%(P <0.01), 并在 7 d 的随访期中保持稳定。组织放射微成像和组织病理学分析都证实植入的 BMSCs 主要分布于由注射针头插入损伤或慢性心肌梗死所造成的纤维瘢痕组织中。结论心肌内细胞移植术后 7 d 内,被植入到慢性梗死心肌中的 BMSCs 细胞的可利用度高于被植入在正常心肌中的 BMSCs 细胞的可利用度。植入心肌内的 BMSCs 主要分布于由注射针头插入损伤和慢性心肌梗死导致的纤维瘢痕组织中。

Short-term cell availability and distribution of intramyocardial engrafted mesenchymal stem cells in normal and chronic infarcted myocardium

Objective]To investigate the short-term cell availability and cell distribution of 111 Indirm-oxine labeled bone marrow mesenchymal stem cells (BMSCs) intramyocardial transplanted in the normal and chronic infarcted myocardium.Methods]Myocardial infarction was created in the rats model (n=9) with selective coronary arteryligation. One mouth later, 111Indium-oxine labeled autologous BMSCs(2×106 cells in 50 μL) were injected into the chronic infarcted myocardium and the normal control(n=6).Cardiac specific radioactivity was assessed by serial planar pinhole scintigraphy at 2 hour,1,3,and 7 days after BMSCs transplantation,cell retention rate in myocardium was calculated. Cell distribution in myocardium was observed by micro-imaging of myocardial tissue specific radioactivity and histo-pathological analysis, performed on the transverse sryosections of the hearts harvested at 7th day.Results]The cardiac uptake of 111Indium in MI group was significantly (P＜0.001) higher than the control group at each time-point. When measured cardiac specific radioactivity was corrected according to the spontaneous leakage rates of 111Indium from labeled BMSCs,the myocardial retention of BMSCs determined in vitro at each corresponding time-point was about 60% in chronic infarcted myocardium, but only 25% when cells were injected into the normal myocardium (P＜0.01),and these values were consistent during 7 days follow-up period. Micro-imaging and histo-pathological analysis confirmed that transplanted BMSCs located predominantly in the fibrosis zones created by needle insertionor chronic myocardial infarction. Conclusions] Intramyocardial engrafted BMSCs predominantly locate in the fibrous scar tissue of myocardium damaged by needle insertion or chronic myocardial infarction, and the cell availability is higher when they are implanted into the chronic infarcted myocardium than they are engrafted into the normal myocardium, atleast for 7 days after cell transplantation.