Isolation and Enrichment of Circulating Fetal Cells for NIPD: An Overview

Overview

Journal Diagnostics (Basel)

Specialty Radiology

Date 2021 Dec 24

PMID 34943476

Citations 8

Authors

Giulia Sabbatinelli

Donatella Fantasia

Chiara Palka

Elisena Morizio

Melissa Alfonsi

Giuseppe Calabrese

Affiliations

Soon will be listed here.

Abstract

Prenatal diagnosis plays a crucial role in clinical genetics. Non-invasive prenatal diagnosis using fetal cells circulating in maternal peripheral blood has become the goal of prenatal diagnosis, to obtain complete fetal genetic information and avoid risks to mother and fetus. The development of high-efficiency separation technologies is necessary to obtain the scarce fetal cells from the maternal circulation. Over the years, multiple approaches have been applied, including choice of the ideal cell targets, different cell recovering technologies, and refined cell isolation yield procedures. In order to provide a useful tool and to give insights about limitations and advantages of the technologies available today, we review the genetic research on the creation and validation of non-invasive prenatal diagnostic testing protocols based on the rare and labile circulating fetal cells during pregnancy.

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References

Chen F, Liu P, Gu Y, Zhu Z, Nanisetti A, Lan Z . Isolation and whole genome sequencing of fetal cells from maternal blood towards the ultimate non-invasive prenatal testing. Prenat Diagn. 2017; 37(13):1311-1321. DOI: 10.1002/pd.5186. View

Bianchi D, Simpson J, Jackson L, Elias S, Holzgreve W, Evans M . Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn. 2002; 22(7):609-15. DOI: 10.1002/pd.347. View

Benirschke K . Anatomical relationship between fetus and mother. Ann N Y Acad Sci. 1994; 731:9-20. DOI: 10.1111/j.1749-6632.1994.tb55744.x. View

Sargent I, Choo Y, Redman C . Isolating and analyzing fetal leukocytes in maternal blood. Ann N Y Acad Sci. 1994; 731:147-53. DOI: 10.1111/j.1749-6632.1994.tb55761.x. View

Parks D, Herzenberg L . Fetal cells from maternal blood: their selection and prospects for use in prenatal diagnosis. Methods Cell Biol. 1982; 26:277-95. DOI: 10.1016/s0091-679x(08)61370-9. View

van Wijk I, Griffioen S, Tjoa M, Mulders M, van Vugt J, Loke Y . HLA-G expression in trophoblast cells circulating in maternal peripheral blood during early pregnancy. Am J Obstet Gynecol. 2001; 184(5):991-7. DOI: 10.1067/mob.2001.112973. View

Calabrese G, Fantasia D, Alfonsi M, Morizio E, Celentano C, Guanciali Franchi P . Aneuploidy screening using circulating fetal cells in maternal blood by dual-probe FISH protocol: a prospective feasibility study on a series of 172 pregnant women. Mol Genet Genomic Med. 2016; 4(6):634-640. PMC: 5118208. DOI: 10.1002/mgg3.249. View

Kolvraa S, Singh R, Normand E, Qdaisat S, Van den Veyver I, Jackson L . Genome-wide copy number analysis on DNA from fetal cells isolated from the blood of pregnant women. Prenat Diagn. 2016; 36(12):1127-1134. DOI: 10.1002/pd.4948. View

Kleihauer E, Braun H, Betke K . [Demonstration of fetal hemoglobin in erythrocytes of a blood smear]. Klin Wochenschr. 1957; 35(12):637-8. DOI: 10.1007/BF01481043. View

10.

Johnson P, Molloy C . Localization in human term placental bed and amniochorion of cells bearing trophoblast antigens identified by monoclonal antibodies. Am J Reprod Immunol (1980). 1983; 4(1):33-7. DOI: 10.1111/j.1600-0897.1983.tb00250.x. View

11.

Boyer S, Noyes A, Boyer M . Enrichment of erythrocytes of fetal origin from adult-fetal blood mixtures via selective hemolysis of adult blood cells: an aid to antenatal diagnosis of hemoglobinopathies. Blood. 1976; 47(6):883-97. View

12.

Mikhail A, Covic A, Goldsmith D . Stimulating erythropoiesis: future perspectives. Kidney Blood Press Res. 2008; 31(4):234-46. DOI: 10.1159/000141928. View

13.

Guetta E, Gutstein-Abo L, Barkai G . Trophoblasts isolated from the maternal circulation: in vitro expansion and potential application in non-invasive prenatal diagnosis. J Histochem Cytochem. 2005; 53(3):337-9. DOI: 10.1369/jhc.4B6426.2005. View

14.

Burschyk M, Garritsen H, Helmer L, Miny P, Horst J, Schneider H . Magnetic cell sorting and the transferrin receptor as potential means of prenatal diagnosis from maternal blood. Am J Obstet Gynecol. 1992; 166(5):1350-5. DOI: 10.1016/0002-9378(92)91603-8. View

15.

von Koskull H, Gahmberg N . Fetal erythroblasts from maternal blood identified with 2,3-bisphosphoglycerate (BPG) and in situ hybridization (ISH) using Y-specific probes. Prenat Diagn. 1995; 15(2):149-54. DOI: 10.1002/pd.1970150207. View

16.

Sun Y, Cai B, Wei X, Wang Z, Rao L, Meng Q . A valve-based microfluidic device for on-chip single cell treatments. Electrophoresis. 2018; 40(6):961-968. DOI: 10.1002/elps.201800213. View

17.

Klonisch T, Drouin R . Fetal-maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease. Trends Mol Med. 2009; 15(11):510-8. DOI: 10.1016/j.molmed.2009.09.002. View

18.

Campagnoli C, Roberts I, Kumar S, Bennett P, Bellantuono I, Fisk N . Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001; 98(8):2396-402. DOI: 10.1182/blood.v98.8.2396. View

19.

de Graaf I, Jakobs M, Leschot N, Ravkin I, Goldbard S, Hoovers J . Enrichment, identification and analysis of fetal cells from maternal blood: evaluation of a prenatal diagnosis system. Prenat Diagn. 1999; 19(7):648-52. DOI: 10.1002/(sici)1097-0223(199907)19:7<648::aid-pd600>3.0.co;2-x. View

20.

Guanciali Franchi P, Palka C, Morizio E, Sabbatinelli G, Alfonsi M, Fantasia D . Sequential combined test, second trimester maternal serum markers, and circulating fetal cells to select women for invasive prenatal diagnosis. PLoS One. 2017; 12(12):e0189235. PMC: 5720779. DOI: 10.1371/journal.pone.0189235. View