Transfer of fetal cells with multilineage potential to maternal tissue
Transfer of fetal cells with multilineage potential to maternal tissue
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DOI：
10.1001/jama.292.1.75
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发表时间：
2004-07-07
影响因子：
120.7
通讯作者：
Bianchi, DW
中科院分区：
文献类型：
--
作者：
Khosrotehrani, K;Johnson, KL;Bianchi, DW
在怀孕期间，胎儿CD34（+）细胞进入母体循环，持续数十年，并产生生理性微嵌合状态。许多研究证实，妊娠后母体血液和组织中仍存在胎儿细胞。胎儿细胞可能通过在母体器官中发展多谱系能力来应对母体损伤。目的证实胎儿微嵌合细胞在母体器官内表达上皮细胞、白细胞和肝细胞分化标志物。设计、设置和患者：我们收集了10名有男性后代的女性的存档石蜡包埋组织切片标本，这些女性之前发现有大量的微嵌合细胞，另外11名对照女性之前没有怀孕过男性。使用X和Y染色体特异性探针，通过荧光原位杂交鉴定雄性细胞，然后使用抗细胞角蛋白（AE1/AE3）作为上皮细胞标记物，抗cd45作为白细胞标记物，hepar -1作为肝细胞标记物进行组织学和免疫化学研究。主要结局指标表达非造血标志物的微嵌合细胞百分比。结果共鉴定出701个雄性（XY+）嵌合细胞（平均[SD]，每百万母细胞中有227[128]个XY+细胞）。在母体上皮组织（甲状腺、宫颈、肠和胆囊）中，14% - 60%的XY+细胞表达细胞角蛋白。相反，在造血组织中，如淋巴结和脾脏，90%的XY+细胞表达CD45。在1例肝脏样本中，4%的XY+细胞表达hepar -1。独立观察人员评估的组织学和免疫化学分化证据高度一致（kappa = 0.72）。结论在多种母体组织标本中检测到携带上皮细胞、白细胞或肝细胞标记的微嵌合雄性细胞，表明胎儿细胞可能具有多谱系能力。
Context During pregnancy, fetal CD34(+) cells enter the maternal circulation, persist for decades, and create a state of physiologic microchimerism. Many studies have confirmed the residual presence of fetal cells in maternal blood and tissues following pregnancy. Fetal cells may respond to maternal injury by developing multilineage capacity in maternal organs.Objective To verify that fetal microchimeric cells express markers of epithelial, leukocyte, and hepatocyte differentiation within maternal organs.Design, Setting, and Patients Archived paraffin-embedded tissue section specimens from 10 women who had male offspring and were previously found to have high numbers of microchimeric cells, and 11 control women who had no prior male pregnancies. Male cells were identified by fluorescence in situ hybridization, using X and Y chromosome-specific probes, followed by histologic and immunochemical studies using anticytokeratin (AE1/AE3) as a marker of epithelial cells, anti-CD45 as a leukocyte marker, and heppar-1 as a hepatocyte marker.Main Outcome Measure Percentage of microchimeric cells expressing nonhematopoietic markers.Results A total of 701 male (XY+) microchimeric cells were identified (mean [SD], 227 [128] XY+ cells per million maternal cells). In maternal epithelial tissues (thyroid, cervix, intestine, and gallbladder), 14% to 60% of XY+ cells expressed cytokeratin. Conversely, in hematopoietic tissues, such as lymph nodes and spleen, 90% of XY+ cells expressed CD45. In 1 liver sample, 4% of XY+ cells expressed heppar-1. Histologic and immunochemical evidence of differentiation, as assessed by independent observers, was highly concordant (kappa = 0.72).Conclusion The detection of microchimeric male cells, bearing epithelial, leukocyte, or hepatocyte markers, in a variety of maternal tissue specimens suggests the presence of fetal cells that may have multilineage capacity.