Fujiki Yutaka, Johnson Kirby L, Peter Inga, Tighiouart Hocine, Bianchi Diana W
Division of Genetics, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts 02111, USA.
Biol Reprod. 2009 Jul;81(1):26-32. doi: 10.1095/biolreprod.108.074468. Epub 2009 Mar 11.
To better understand fetomaternal cell trafficking during pregnancy, we used a mouse model to determine the cell surface markers expressed on fetal cells, based on the hypothesis that fetal progenitor cells have the capacity to repair maternal organs, whereas more differentiated cells might initiate graft versus host disease. Wild-type females were mated to either homozygous or hemizygous transgenic males and euthanized in the peripartum period. Using dual color flow cytometry, we analyzed fetal transgene positive cells for the presence of nine markers (ITGAM, ITGB1, PECAM, CD34, CD44, PTPRC, ENG, SLAMF1, and CXCR4) to begin to identify the phenotype and degree of differentiation of fetal cells in nine maternal organs (lung, liver, spleen, blood, bone marrow, kidney, heart, thymus, and brain). Fetal cells were found in all maternal organs following either type of mating, albeit always at a higher frequency following mating with homozygous males. Some organs (e.g., lung and liver) had a wide variety of fetal cell markers present, while other organs (e.g., bone marrow and spleen) had a skewed distribution of fetal cell markers. Fetal cells in the murine pregnant female are diverse. Our results suggest that the fetal cells comprise a mixed population of progenitor and differentiated cells, with different relative proportions in different maternal organs. Future studies will address whether fetal cells cross the placental barrier in a differentiated state or as a homogenous population and subsequently differentiate in target maternal organs.
为了更好地理解孕期母胎细胞转运,我们基于胎儿祖细胞有修复母体器官的能力,而分化程度更高的细胞可能引发移植物抗宿主病这一假设,使用小鼠模型来确定胎儿细胞上表达的细胞表面标志物。野生型雌性小鼠与纯合或半合子转基因雄性小鼠交配,并在围产期实施安乐死。我们使用双色流式细胞术分析胎儿转基因阳性细胞中九种标志物(整合素αM、整合素β1、血小板内皮细胞黏附分子、CD34、CD44、蛋白酪氨酸磷酸酶C、内皮糖蛋白、信号淋巴细胞激活分子家族成员1和CXC趋化因子受体4)的存在情况,以初步确定胎儿细胞在九个母体器官(肺、肝、脾、血液、骨髓、肾、心脏、胸腺和脑)中的表型和分化程度。无论哪种交配类型,在所有母体器官中均发现了胎儿细胞,不过与纯合雄性小鼠交配后胎儿细胞的出现频率总是更高。一些器官(如肺和肝)存在多种胎儿细胞标志物,而其他器官(如骨髓和脾)的胎儿细胞标志物分布则不均衡。小鼠怀孕母体内的胎儿细胞具有多样性。我们的结果表明,胎儿细胞由祖细胞和分化细胞组成的混合群体构成,在不同母体器官中的相对比例各不相同。未来的研究将探讨胎儿细胞是以分化状态还是以同质群体的形式穿过胎盘屏障,以及随后在目标母体器官中是否会发生分化。