Mount Sinai School of Medicine, Cardiovascular Institute, New York, New York, USA.
Clin Transl Sci. 2012 Aug;5(4):321-8. doi: 10.1111/j.1752-8062.2012.00424.x. Epub 2012 Jun 18.
Fetal cells enter the maternal circulation during pregnancies and can persist in blood and tissues for decades, creating a state of physiologic microchimerism. Microchimerism refers to acquisition of cells from another individual and can be due to bidirectional cell traffic between mother and fetus during pregnancy. Peripartum cardiomyopathy, a rare cardiac disorder associated with high mortality rates has the highest recovery rate amongst all etiologies of heart failure although the reason is unknown. Collectively, these observations led us to hypothesize that fetal cells enter the maternal circulation and may be recruited to the sites of myocardial disease or injury. The ability to genetically modify mice makes them an ideal system for studying the phenomenon of microchimerism in cardiac disease. Described here is a mouse model for ischemic cardiac injury during pregnancy designed to study microchimerism. Wild-type virgin female mice mated with eGFP male mice underwent ligation of the left anterior descending artery to induce a myocardial infarction at gestation day 12. We demonstrate the selective homing of eGFP cells to the site of cardiac injury without such homing to noninjured tissues suggesting the presence of precise signals sensed by fetal cells enabling them to target diseased myocardium specifically.
胎儿细胞在妊娠期间进入母体循环,并可在血液和组织中持续存在数十年,形成生理性嵌合体状态。嵌合体是指从另一个个体获得细胞,这可能是由于妊娠期间母亲和胎儿之间的双向细胞迁移。围产期心肌病是一种罕见的与高死亡率相关的心脏疾病,尽管原因不明,但它是心力衰竭所有病因中恢复率最高的。综上所述,这些观察结果使我们假设胎儿细胞进入母体循环,并可能被招募到心肌疾病或损伤部位。能够对小鼠进行基因修饰使它们成为研究心脏疾病中嵌合体现象的理想系统。这里描述的是一种在妊娠期间用于研究缺血性心脏损伤的小鼠模型,用于研究嵌合体。与 eGFP 雄性小鼠交配的野生型处女雌性小鼠在妊娠第 12 天结扎左前降支以诱导心肌梗死。我们证明了 eGFP 细胞选择性归巢到心脏损伤部位,而不会归巢到未受伤的组织,这表明胎儿细胞感知到了精确的信号,使它们能够特异性地靶向患病的心肌。