UNIVERSITEIT TWENTE;KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN
发明人:
RIVRON, Nicolas Clément,VAN BLITTERSWIJK, Clemens Antoni,GEIJSEN, Niels,VRIJ, Erik Jacob
申请号：
NLNL2014/050239
公开号：
WO2014/171824A1
申请日:
2014.04.16
申请国别(地区):
NL
年份:
2014
代理人:
摘要：
The invention relates to a method for making an at least double layered cell aggregate and/or an artificial blastocyst, and/or a further-developed blastoid termed blastoid, by forming a double layered cell aggregate from at least one trophoblast cell and at least one pluripotent and/or totipotent cell, and culturing said aggregate to obtain an artificial blastocyst. This artificial blastocyst has a trophectoderm-like tissue that surrounds a blastocoel and an inner cell mass-like tissue. The cell aggregate can be formed from toti- or pluripotent stem cell types, or induced pluripotent stem cell types, in combination with trophoblast stem cells. Formation of a blastoid can be achieved by culturing the cell aggregate in a medium preferably comprising one or more of a Rho/ROCK inhibitor, a Wnt pathway modulator, a PKA pathway modulator, a PKC pathway modulator, a MAPK pathway modulator, a STAT pathway modulator, an Akt pathway modulator, a Tgf pathway modulator and a Hippo pathway modulator. The invention further relates to a method for growing an at least double layered cell aggregate into an artificial blastocyst, and into a further-developed blastoid, a fetus or a live animal. The invention further pertains to an in vitro cell culture comprising the mentioned compounds and/or cell aggregates.L'invention concerne un procédé de fabrication d'un agrégat cellulaire ayant au moins deux couches et/ou un blastocyste artificiel et/ou un blastoïde davantage développé appelé blastoïde, par la formation d'un agrégat cellulaire à deux couches à partir d'au moins une cellule de trophoblaste et au moins une cellule pluripotente et/ou totipotente, et la culture dudit agrégat pour obtenir un blastocyste artificiel. Ce blastocyste artificiel a un tissu de type trophectoderme qui entoure un blastocoèle et un tissu de type masse cellulaire interne. L'agrégat cellulaire peut être formé à partir de types de cellules souches toti-ou pluripotentes ou des types de cellules souches pluripote
