Mikhail Magued A, M'Hamdi Hanane, Welsh Jonathan, Levicar Natasa, Marley Stephen B, Nicholls Joanna P, Habib Nagy A, Louis Louay S, Fisk Nicholas M, Gordon Myrtle Y
Department of Surgery, Imperial College London, Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Hum Reprod. 2008 Apr;23(4):928-33. doi: 10.1093/humrep/dem417. Epub 2008 Jan 31.
During pregnancy, fetal cells enter the maternal bloodstream resulting in fetal cell microchimerism. The fetal cells persist in the mother for decades and colonize a variety of maternal organs. They are associated with maternal autoimmune diseases and may also participate in tissue repair. The identity of the microchimeric cells is not certain but they must be able to persist long-term and have potential for multitissue differentiation.
Here we tested the hypothesis that the fetal microchimeric cells are primitive stem cells, represented by CD34+ adherent cells, which have a wide potential for differentiation. We isolated these stem cells from the blood of pregnant females (n = 25) and detected fetal cells of the correct gender, using fluorescence in situ hybridization, in a high proportion (71% male fetuses and 90% female fetuses; false positive rate 11%, false negative rate 29%) of cases. By RT-PCR, we demonstrated that the cells express Oct-4, Nanog and Rex-1. No fetal cells were detected in the mononuclear or total CD34+ cell populations but high frequencies (mean 11.8%) of fetal cells were detected in the adherent CD34+ cell population.
These results identify adherent CD34+ stem cells as candidate fetal microchimeric cells, which are capable of sustaining the fetal cell population in the long term and have the ability to colonize multiple tissues and organs.
孕期,胎儿细胞进入母体血液循环,导致胎儿细胞微嵌合体现象。胎儿细胞可在母亲体内持续数十年,并在多种母体器官中定植。它们与母体自身免疫性疾病相关,还可能参与组织修复。微嵌合细胞的身份尚不确定,但它们必须能够长期存活并具有多组织分化的潜力。
在此,我们检验了这样一个假设,即胎儿微嵌合细胞是以CD34 + 贴壁细胞为代表的原始干细胞,具有广泛的分化潜力。我们从25名怀孕女性的血液中分离出这些干细胞,并使用荧光原位杂交技术在高比例(71% 的男性胎儿和90% 的女性胎儿;假阳性率11%,假阴性率29%)的病例中检测到了性别正确的胎儿细胞。通过逆转录聚合酶链反应,我们证明这些细胞表达Oct-4、Nanog和Rex-1。在单核细胞或总CD34 + 细胞群体中未检测到胎儿细胞,但在贴壁CD34 + 细胞群体中检测到了高频率(平均11.8%)的胎儿细胞。
这些结果确定贴壁CD34 + 干细胞为候选胎儿微嵌合细胞,它们能够长期维持胎儿细胞群体,并具有定植于多个组织和器官的能力。