Artificial Blastocyst Formation via Double-Layered Cell Aggregates
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Solution Overview
Problem
Current methods for generating genetically modified organisms and assessing drug efficacy and toxicity are laborious, resource-intensive, and require the sacrifice of numerous animals, as they rely on in vivo embryo harvesting and breeding, which is ethically and practically challenging.
Innovation Solution
A method to form an artificial blastocyst in vitro using cell lines, specifically by creating a double-layered cell aggregate comprising trophoblast and pluripotent/stotipotent cells, which can be cultured to form a blastoid, allowing for the generation of genetically modified embryos or tissues without the need for in vivo embryo harvesting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If embryos are harvested in vivo from pregnant animals, then genetically modified organisms can be generated, but numerous animals must be sacrificed and the process is laborious and resource-intensive
Solution Approach 1:
The patent creates artificial blastocysts (blastoids) that copy the essential structural and functional characteristics of natural blastocysts without requiring actual embryos. The blastoid comprises an inner cell mass surrounded by a trophectoderm layer, replicating the natural blastocyst structure while eliminating the need to harvest and sacrifice animals for research and genetic modification purposes
Solution Approach 2:
The patent extracts and separates the essential components of a natural blastocyst (inner cell mass and trophectoderm) and reconstructs them in vitro as an artificial blastocyst. This extraction approach allows the formation of functional blastoids without using actual embryos, thereby avoiding animal sacrifice while maintaining the necessary biological structures for genetic modification and research
2Productivity
If natural embryos are used for genetic modification, then genetically modified organisms can be produced, but the process requires lengthy breeding programs and is difficult
Solution Approach 1:
The patent performs genetic modifications on the artificial blastoid at an early stage before implantation, allowing for direct manipulation of the developing organism without requiring lengthy breeding programs. The artificial blastocyst can be genetically modified in vitro and then implanted, eliminating the need for complex selective breeding to achieve desired genetic traits
Solution Approach 2:
The artificial blastoid serves as an intermediary structure that bridges the gap between in vitro cell culture and in vivo organism development. It provides a controlled platform for genetic modification that can be directly implanted into a host, eliminating the need for complex breeding programs while maintaining the ability to produce genetically modified organisms
3Quantity of substance
If embryos are harvested from pregnant animals, then embryonic structures can be obtained for research, but the embryonic structure is disrupted and cannot become a live animal
Solution Approach 1:
The patent creates artificial blastocysts that copy the essential structure and function of natural blastocysts without harvesting them from pregnant animals. The blastoid comprises an inner cell mass surrounded by a trophectoderm layer, replicating the natural structure while maintaining viability and the ability to develop into a live animal without disrupting a pregnant host
4Ease of manufacture
If in vitro embryo formation is attempted, then animal testing can be performed, but current methods cannot form complete blastocysts or placental tissues
Solution Approach 1:
The patent merges the capabilities of different cell types (inner cell mass cells and trophectoderm cells) into a single artificial blastocyst structure. This combination allows the blastoid to form both embryonic tissues and extraembryonic placental tissues, providing complete tissue formation capability in vitro while enabling comprehensive animal testing models
Data Source
AI summary
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.