Semin Reprod Med 2016; 34(01): 050-056
DOI: 10.1055/s-0035-1570026
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cellular Models of Trophoblast Differentiation

Marissa L. Steinberg
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
,
Jared C. Robins
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
› Author Affiliations
Further Information

Publication History

Publication Date:
11 January 2016 (online)

Abstract

Orchestrated trophoblast differentiation is necessary to establish and maintain a normal pregnancy, however the molecular mechanisms that guide this process remain largely unknown. Although early studies of cytotrophoblast differentiation relied on animal models, more recent trophoblast research has involved in vitro models of human tissue. These in vitro models have utilized cultured trophoblast cell lines, primary cell culture, and villous explant cultures–each with its advantages and disadvantages. Traditionally, attempts to develop in vitro models of human placental differentiation have relied on two-dimensional cell culture. Though monolayer culture methods have been refined over time this technique has several limitations, including the inability to study cell-to-cell interactions. Recently, several studies have employed three-dimensional culture methods to overcome many of the limitations of traditional two-dimensional trophoblast culture. These three-dimensional culture systems have an important role in both the study of cytotrophoblast differentiation and development of new therapeutics targeting placenta associated diseases.

 
  • References

  • 1 Lyall F. Mechanisms regulating cytotrophoblast invasion in normal pregnancy and pre-eclampsia. Aust N Z J Obstet Gynaecol 2006; 46 (4) 266-273
  • 2 Norwitz ER. Defective implantation and placentation: laying the blueprint for pregnancy complications. Reprod Biomed Online 2006; 13 (4) 591-599
  • 3 Graham CH, Lala PK. Mechanisms of placental invasion of the uterus and their control. Biochem Cell Biol 1992; 70 (10–11) 867-874
  • 4 Damsky CH, Fitzgerald ML, Fisher SJ. Distribution patterns of extracellular matrix components and adhesion receptors are intricately modulated during first trimester cytotrophoblast differentiation along the invasive pathway, in vivo. J Clin Invest 1992; 89 (1) 210-222
  • 5 Morrish DW, Dakour J, Li H. Functional regulation of human trophoblast differentiation. J Reprod Immunol 1998; 39 (1–2) 179-195
  • 6 Borbely AU, Sandri S, Fernandes IR , et al. The term basal plate of the human placenta as a source of functional extravillous trophoblast cells. Reprod Biol Endocrinol 2014; 12: 7
  • 7 Orendi K, Kivity V, Sammar M , et al. Placental and trophoblastic in vitro models to study preventive and therapeutic agents for preeclampsia. Placenta 2011; 32 (Suppl): S49-S54
  • 8 Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nat Rev Immunol 2006; 6 (8) 584-594
  • 9 Niwa H, Toyooka Y, Shimosato D , et al. Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell 2005; 123 (5) 917-929
  • 10 Carter AM. Animal models of human placentation–a review. Placenta 2007; 28: 41-47
  • 11 Jollie WP. Development, morphology, and function of the yolk-sac placenta of laboratory rodents. Teratology 1990; 41 (4) 361-381
  • 12 King A, Thomas L, Bischof P. Cell culture models of trophoblast II: trophoblast cell lines—a workshop report. Placenta 2000; 21 (Suppl A): S113-S119
  • 13 Wolfe MW. Culture and transfection of human choriocarcinoma cells. Methods Mol Med 2006; 121: 229-239
  • 14 Hertz R. Choriocarcinoma of women maintained in serial passage in hamster and rat. Proc Soc Exp Biol Med 1959; 102: 77-81
  • 15 Pattillo RA, Gey GO. The establishment of a cell line of human hormone-synthesizing trophoblastic cells in vitro. Cancer Res 1968; 28 (7) 1231-1236
  • 16 Soares MJ, Hunt JS. Placenta and Trophoblast: Methods and Protocols. Totowa, NJ: Humana Press; 2006
  • 17 Kilburn BA, Wang J, Duniec-Dmuchowski ZM, Leach RE, Romero R, Armant DR. Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line. Biol Reprod 2000; 62 (3) 739-747
  • 18 Graham CH, Postovit LM, Park H, Canning MT, Fitzpatrick TE. Adriana and Luisa Castellucci award lecture 1999: role of oxygen in the regulation of trophoblast gene expression and invasion. Placenta 2000; 21 (5–6) 443-450
  • 19 Lewis MP, Clements M, Takeda S , et al. Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop. Placenta 1996; 17 (2–3) 137-146
  • 20 Shiverick KT, King A, Frank H, Whitley GS, Cartwright JE, Schneider H. Cell culture models of human trophoblast II: trophoblast cell lines—a workshop report. Placenta 2001; 22 (Suppl A): S104-S106
  • 21 Li JN, Ge YC, Yang Z , et al. The Sp1 transcription factor is crucial for the expression of 11beta-hydroxysteroid dehydrogenase type 2 in human placental trophoblasts. J Clin Endocrinol Metab 2011; 96 (6) E899-E907
  • 22 Robins JC, Heizer A, Hardiman A, Hubert M, Handwerger S. Oxygen tension directs the differentiation pathway of human cytotrophoblast cells. Placenta 2007; 28 (11–12) 1141-1146
  • 23 Douglas GC, VandeVoort CA, Kumar P, Chang TC, Golos TG. Trophoblast stem cells: models for investigating trophectoderm differentiation and placental development. Endocr Rev 2009; 30 (3) 228-240
  • 24 Graham CH, Hawley TS, Hawley RG , et al. Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res 1993; 206 (2) 204-211
  • 25 Rielland M, Hue I, Renard JP, Alice J. Trophoblast stem cell derivation, cross-species comparison and use of nuclear transfer: new tools to study trophoblast growth and differentiation. Dev Biol 2008; 322 (1) 1-10
  • 26 Tanaka S, Kunath T, Hadjantonakis AK, Nagy A, Rossant J. Promotion of trophoblast stem cell proliferation by FGF4. Science 1998; 282 (5396) 2072-2075
  • 27 Rossant J. Stem cells from the mammalian blastocyst. Stem Cells 2001; 19 (6) 477-482
  • 28 Mi S, Lee X, Li X , et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000; 403 (6771) 785-789
  • 29 Robins JC, Morgan JR, Krueger P, Carson SA. Bioengineering anembryonic human trophoblast vesicles. Reprod Sci 2011; 18 (2) 128-135
  • 30 Kelm JM, Ehler E, Nielsen LK, Schlatter S, Perriard JC, Fussenegger M. Design of artificial myocardial microtissues. Tissue Eng 2004; 10 (1–2) 201-214
  • 31 Martin I, Wendt D, Heberer M. The role of bioreactors in tissue engineering. Trends Biotechnol 2004; 22 (2) 80-86
  • 32 Gordon JNW, Shu WP, Schlussel RN, Droller MJ, Liu BC. Altered extracellular matrices influence cellular processes and nuclear matrix organizations of overlying human bladder urothelial cells. Cancer Res 1993; 53 (20) 4971-4977
  • 33 Wendt D, Stroebel S, Jakob M, John GT, Martin I. Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions. Biorheology 2006; 43 (3–4) 481-488
  • 34 Timmins NE, Harding FJ, Smart C, Brown MA, Nielsen LK. Method for the generation and cultivation of functional three-dimensional mammary constructs without exogenous extracellular matrix. Cell Tissue Res 2005; 320 (1) 207-210
  • 35 Keller GM. In vitro differentiation of embryonic stem cells. Curr Opin Cell Biol 1995; 7 (6) 862-869
  • 36 Korff T, Krauss T, Augustin HG. Three-dimensional spheroidal culture of cytotrophoblast cells mimics the phenotype and differentiation of cytotrophoblasts from normal and preeclamptic pregnancies. Exp Cell Res 2004; 297 (2) 415-423
  • 37 LaMarca HL, Ott CM, Höner Zu Bentrup K , et al. Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion. Placenta 2005; 26 (10) 709-720
  • 38 Foty RA, Steinberg MS. The differential adhesion hypothesis: a direct evaluation. Dev Biol 2005; 278 (1) 255-263
  • 39 Miller RK, Genbacev O, Turner MA, Aplin JD, Caniggia I, Huppertz B. Human placental explants in culture: approaches and assessments. Placenta 2005; 26 (6) 439-448
  • 40 Mehendale R, Hibbard J, Fazleabas A, Leach R. Placental angiogenesis markers sFlt-1 and PlGF: response to cigarette smoke. Am J Obstet Gynecol 2007; 197 (4) 363.e1-363.e5
  • 41 Robinson NJ, Wareing M, Hudson NK , et al. Oxygen and the liberation of placental factors responsible for vascular compromise. Lab Invest 2008; 88 (3) 293-305