3D Endometrium Assembloid Culture for In Vitro Embryo Implantation
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Solution Overview
Problem
The high incidence of implantation failure in human embryos, particularly in IVF procedures, is a significant challenge due to the lack of suitable models to study this stage, as existing culture conditions do not allow embryos to undergo implantation outside their physiological environment, hindering the understanding of molecular and cellular mechanisms and limiting the development of agents to enhance or hinder implantation.
Innovation Solution
A three-dimensional endometrium assembloid is created by growing endometrial stromal cells in a hydrogel matrix and layering endometrial epithelial organoids on top, comprising components like dextran polymers, cyclodextrin crosslinkers, collagen I, collagen III, collagen VI, and fibronectin, which supports embryo implantation and development in vitro.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional culture conditions are used, then embryos can be maintained in vitro, but they cannot undergo implantation outside their physiological environment
Solution Approach 1:
The patent uses an endometrial assembloid as an intermediary structure that mediates between the embryo and the artificial culture environment. The assembloid, composed of stromal cells in a hydrogel matrix with epithelial organoids layered on top, provides the necessary physiological cues for embryo implantation without requiring the complex in vivo uterine environment.
Solution Approach 2:
The invention changes the physical and biochemical parameters of the culture system by using a hydrogel matrix with specific mechanical properties (mimicking endometrial stroma) and incorporating living endometrial cells that secrete physiological factors. This transforms the culture environment from a simple chemical medium to a complex, dynamic system that supports implantation.
2Loss of information
If histological examinations of hysterectomies are used, then insights into cytoarchitecture are obtained, but deep understanding of molecular and cellular mechanisms is prevented
Solution Approach 1:
The patent creates an in vitro copy of the endometrial tissue environment using Assembloids that replicate the structural and functional features of the native endometrium. This copying approach allows researchers to study implantation mechanisms in a controlled setting without relying on scarce histological specimens, thereby preserving and enabling access to molecular and cellular information.
3Reliability
If multiple IVF cycles are required due to implantation failure, then live birth chances decrease, but no suitable models exist to study implantation mechanisms
Solution Approach 1:
The endometrial assembloid system provides a controllable feedback mechanism for studying implantation. Researchers can manipulate variables in the assembloid culture and observe the effects on embryo implantation, creating a feedback loop that enables systematic investigation of implantation mechanisms and identification of factors influencing success rates.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The assembloid recapitulates the structural and functional features of the human endometrium, allowing human embryos to implant and develop in vitro, enabling the study of implantation mechanisms and screening for agents that modulate implantation.
Implementation Method 1
growing endometrial stromal cells inside a hydrogel matrix
Implementation Method 2
the hydrogel matrix comprises one or more of the following components: dextran polymers, cyclodextrin crosslinkers comprising matrix metalloprotease cleavable sites, collagen I, collagen III, collagen VI and fibronectin
Data Source
AI summary
The invention relates to a method of generating an in vitro endometrium assembloid comprising growing endometrial stromal cells inside a hydrogel matrix and layering cells and/or fragments from endometrial epithelial organoids on top, thereby generating a three-dimensional endometrium assembloid comprising a stromal compartment, an outer luminal epithelial layer and a functional secretory glandular endometrium. The invention further relates to an in vitro endometrium assembloid produced according to the methods defined herein. Also provided are methods for determining embryo implantation ability and/or window of receptibility to embryo implantation and for screening for embryo implantation-modulating agents comprising, providing the in vitro endometrium assembloid defined herein. The invention further relates to the use of three sequential human embryo media (HEM) for culturing human stem cell based embryo-like (blastoids) or human blastocysts, and to the compositions of the three media.