Parthenogenetic Activation of Human Oocytes for Stem Cell Production

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Solution Overview

Problem

Current methods for obtaining human embryonic stem cells face ethical concerns and inefficiencies, particularly in sourcing and the low success rate of parthenogenetic activation of oocytes, which limits the production of differentiated cells suitable for therapeutic applications.

Innovation Solution

A method involving parthenogenetic activation of human oocytes using specific conditions, including high oxygen tension with an ionophore and low oxygen tension with a serine-threonine kinase inhibitor, followed by cultivation and isolation of inner cell masses, to produce autologous stem cells that are substantially identical to the donor, avoiding immune rejection and ethical concerns.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If conventional methods are used to obtain human embryonic stem cells from blastocysts or nuclear transfer, then stem cells can be produced, but ethical concerns arise and the process becomes complex

Engineering Contradiction:

Improveease of stem cell productionVSAvoidethical concerns

Core Design Contradiction:

Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the harmful ethical element by removing the need for fertilization and embryo destruction. Instead of obtaining stem cells from fertilized blastocysts or nuclear transfer, the invention uses parthenogenetic activation of unfertilized oocytes, thereby extracting the stem cell production process from the ethical controversy surrounding traditional methods

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent creates a copy of the embryonic development process without requiring actual fertilization. By inducing parthenogenetic activation, the oocyte undergoes developmental changes similar to fertilized embryos, producing inner cell masses that can be cultured as stem cells, thus copying the essential features of embryonic stem cell production without the ethical issues

Inventive Principle:

Principle #26Copying

2Productivity

If parthenogenetic activation is attempted with conventional methods, then stem cell production is possible, but the success rate is low

Engineering Contradiction:

Improvestem cell production rateVSAvoidsuccess rate of activation

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by optimizing the activation protocol with specific combinations of chemicals (ionophore A23187, cycloheximide, 6-DIMETHYLAMINOPURINE), temperatures (37°C), and oxygen tensions (5% O2). These parameter optimizations significantly improve the reliability and success rate of parthenogenetic activation compared to conventional methods

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs preliminary action by pre-treating oocytes with specific chemicals before activation and maintaining them under optimized culture conditions. The use of cycloheximide and other agents in preliminary treatment steps prepares the oocytes for successful activation and development, thereby improving overall productivity

Inventive Principle:

Principle #10Preliminary action

3Productivity

If oxygen tension is not optimized during oocyte activation and cultivation, then the process is simpler, but the development rate and stem cell quality decrease

Engineering Contradiction:

Improvedevelopment rateVSAvoidcomplexity of culture conditions

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by establishing specific oxygen tension conditions (5% O2) during different stages of oocyte activation and blastocyst development. This parameter optimization significantly improves development rates and stem cell quality, demonstrating that controlled complexity in culture conditions yields substantial productivity gains

Inventive Principle:

Principle #35Parameter changes

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

This method efficiently produces autologous stem cells that can differentiate into various cell types, overcoming ethical issues and improving the success rate of stem cell production, enabling therapeutic applications with reduced immune rejection.

Implementation Method 1

contacting the oocyte with an ionophore at high oxygen (O2) tension

Methodology Applied

Scientific EffectIonophore action:

Implementation Method 2

contacting the oocyte with a serine-threonine kinase inhibitor under low O2 tension

Methodology Applied

Scientific EffectKinase inhibition:

Implementation Method 3

Parthenogenetic activation is the production of embryonic cells, with or without eventual development into an adult, from a female gamete in the absence of any contribution from a male gamete

Methodology Applied

Scientific EffectParthenogenetic activation:

Data Source

PatentUS11324778B2Parthenogenic activation of human oocytes for the production of neuronal cells

Publication Date: 2022.05.10 INT STEM CELL CORP

AI summary

Methods of producing human stem cells are disclosed for parthenogenetically activating human oocytes by manipulation of O2 tension, including manipulation of Ca2+ under high O2 tension and contacting oocytes with serine threonine kinase inhibitors under low O2 tension, isolating inner cell masses (ICMs) from the activated oocytes, and culturing the cells of the isolated ICMs under high O2 tension. Moreover, methods are described for the production of stems cells from activated oocytes in the absence of non-human animal products, including the use of human feeder cells/products for culturing ICM/stem cells. Stem cells produced by the disclosed methods are also described.