Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection

Abstract

Fetal cells occur in maternal blood in a substantial proportion of normal pregnancies. Several different approaches have been used to detect and enrich these cells for non-invasive prenatal diagnosis. However, before these fetal cells can routinely be used for prenatal diagnosis, perfectly reproducible procedures for detection and enrichment need to be established. We found that these fetal cells express high intracellular levels of the DNA precursor pathway enzyme thymidine kinase. Since normal adult peripheral blood cells do not exhibit any thymidine kinase activity, this enzyme is a potent new marker to detect and enrich fetal cells from maternal blood. We further describe the first successful application of a cytofluorometric thymidine kinase assay to detect fetal cells in the maternal circulation by virtue of their high thymidine kinase activity.© 1997 Federation of European Biochemical Societies.

Prenatal Diagnosis of Genetic Abnormalities Using Fetal CD34 + Stem Cells in Maternal Circulation and Evidence They Do Not Affect Diagnosis in Later Pregnancies

“…Further studies will focus on maternal cell suppression and selective "in vitro" culture of fetal cells. Investigations into the best culture time for fetal CD34 + cell growth [29,38], supplements for culture media [41,42], and biological differences between fetal and maternal cells appear to be the most promising approaches [18,43].…”

“…1-13), who had never been pregnant (Nos. [14][15][16][17][18][19][20][21][22][23][24][25], and who were currently pregnant (Nos. [26][27][28][29][30][31][32][33].…”

“…Table 2 shows the efficacy of CD34 + stem cell enrichment in pregnancies with normal (Nos. [15][16][17][18][19] and abnormal fetuses (Nos. [32][33][34][35], as determined by recovery of fetal stem cells.…”

“…Many strategies have been designed to improve the recovery, purity, and yield of these fetal cells from maternal blood, but the success rate varies considerably [11][12][13][14][15][16][17][18]. The major limitations to most of these techniques are the few fetal cells which can be sorted from maternal blood samples [19][20][21][22] and the lack of a specific fetal cell marker [23][24][25].…”

A Comparison of in vitro Culture of Fetal Nucleated Erythroblasts from Fetal Chorionic Villi and Maternal Peripheral Blood for Noninvasive Prenatal Diagnosis

“…Considering that fetal nucleated erythroblasts are rare in the maternal blood, it is essential to develop a reliable and stable approach to isolate sufficient numbers from the maternal blood circulation for noninvasive prenatal diagnosis. Even though several methods such as fluorescence-activated cell sorting (FACS) [12], magnetic-activated cell sorting (MACS) [12], charge-flow separation [13] and lectins [14] have been adopted for the isolation of fetal cells, the reliability and efficiency of these methods remain questionable, limiting their clinical application [8,9,14,15,16,17,18]. To overcome the scarcity of fetal nucleated erythroblasts in the maternal blood, some researchers have attempted to amplify the cell colony by culturing them in vitro [19,20,21,22,23]; however, the feasibility of this culturing process for a clinical operation remains elusive, partly due to the limitation of the technique employed in the experiments [24,25,26].…”