Details

Autor(en) / Beteiligte

• LaMarca, H.L.
• Ott, C.M.
• Höner zu Bentrup, K.
• LeBlanc, C.L.
• Pierson, D.L.
• Nelson, A.B.
• Scandurro, A.B.
• Whitley, G. St. J.
• Nickerson, C.A.
• Morris, C.A.

Titel

Three-dimensional growth of extravillous cytotrophoblasts promotes differentiation and invasion

Ist Teil von

• Placenta (Eastbourne), 2005-11, Vol.26 (10), p.709-720

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2005

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Human trophoblast research relies on a combination of in vitro models, including isolated primary cultures, explant cultures, and trophoblast cell lines. In the present study, we have utilized the rotating wall vessel (RWV) bioreactor to generate a three-dimensional (3-D) model of human placentation for the study of cytotrophoblast (CTB) invasion. The RWV supported the growth of the human CTB cell line SGHPL-4 and allowed for the formation of complex, multilayered 3-D aggregates that were morphologically, phenotypically, and functionally distinct from SGHPL-4 monolayers. The cells cultured three-dimensionally differentiated into an aggressively invasive cell population characterized by the upregulation of matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9 and urokinase-type plasminogen activator (uPA) secretion and activation. Microarray analysis of the 3-D and 2-D cultured cells revealed increased expression in the 3-D cells of various genes that are known mediators of invasion, including MT1-MMP, PECAM-1 and L-selectin, as well as genes not previously associated with CTB differentiation such as MMP-13 and MT5-MMP. These results were verified by quantitative real-time PCR. These findings suggest that when cultured in 3-D, SGHPL-4 cells closely mimic differentiating in utero CTBs, providing a novel approach for the in vitro study of the molecular mechanisms that regulate CTB differentiation and invasion.