Angelini Annalisa, Castellani Chiara, Tona Francesco, Gambino Antonio, Caforio Alida P, Feltrin Giuseppe, Della Barbera Mila, Valente Marialuisa, Gerosa Gino, Thiene Gaetano
Medical-Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy.
J Heart Lung Transplant. 2007 Nov;26(11):1110-8. doi: 10.1016/j.healun.2007.08.004.
The mechanisms of stem cell engraftment and differentiation in transplanted organs are still unknown. The aim of our study was to assess the time course of extracardiac progenitor cell colonization of cardiac allografts using the human sex-mismatched heart transplant model. The possible mechanisms by which stem cells acquire a cardiac phenotypic lineage were also investigated.
Thirty-four endomyocardial biopsies were obtained from 17 sex-mismatched orthotopic heart transplant patients (mean age, 43.50 +/- 23.95 years). Cells of recipient origin were identified by fluorescence in situ hybridization for combined XY-chromosomes.
The mean incremental number of cardiomyocytes of recipient origin per month was 0.064 +/- 0.04, suggesting ongoing engraftment and transdifferentiation in the absence of cell fusion. Regression analysis showed a positive correlation between the Y-chromosome-positive cardiomyocytes and the rejection score (r(2) = 0.99; 95% confidence interval -0.14 + 0.02; p = 0.006) suggesting that colonization was more pronounced in cases of more severe cardiac injury. At multivariable analysis, time since transplantation was the only independent predictor of the proportion of XY-chromosome-positive cardiac cell engraftment (beta = 0.025, p < 0.0001, 95% confidence interval, 0.012-0.038).
The phenotypic transformation in this human chronic heart injury model is the result of transdifferentiation of male stem cells (atrial or circulating cells) into new cardiomyocytes. Immunologic injury predicts recipient cardiomyocyte engraftment and may be one of the mobilizing stimuli.
移植器官中干细胞植入和分化的机制仍不清楚。我们研究的目的是使用人类性别不匹配心脏移植模型评估心脏同种异体移植物中心外膜祖细胞定植的时间进程。还研究了干细胞获得心脏表型谱系的可能机制。
从17例性别不匹配的原位心脏移植患者（平均年龄43.50±23.95岁）中获取34份心内膜活检标本。通过联合XY染色体的荧光原位杂交鉴定受体来源的细胞。
受体来源的心肌细胞每月平均增加数量为0.064±0.04，提示在无细胞融合的情况下持续植入和转分化。回归分析显示Y染色体阳性心肌细胞与排斥反应评分之间呈正相关（r² = 0.99；95%置信区间-0.14 + 0.02；p = 0.006），提示在心脏损伤更严重的病例中定植更明显。在多变量分析中，移植后的时间是XY染色体阳性心脏细胞植入比例的唯一独立预测因素（β = 0.025，p < 0.0001，95%置信区间，0.012 - 0.038）。
在这种人类慢性心脏损伤模型中，表型转化是男性干细胞（心房或循环细胞）转分化为新的心肌细胞的结果。免疫损伤可预测受体心肌细胞植入，可能是动员刺激因素之一。
