Metanephros Freezing for Artificial Kidney Precursor Production

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Solution Overview

Problem

Current methods for producing an artificial kidney precursor are complex, requiring high skill, involve risks of contamination, and lack flexibility in scheduling due to the need for embryo cultivation and biological safety testing, making them unsuitable for simple and safe transplantation.

Innovation Solution

The method involves freezing and thawing a metanephros from an embryo, followed by the transfer of patient-derived mesenchymal stem cells outside the body, allowing for easy biological safety testing and flexible treatment scheduling without the need for cultivation, using a metanephros at an immature MHC expression stage to minimize immune reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mesenchymal stem cells are injected into an embryo to produce artificial kidney precursor, then the precursor can be obtained, but the process becomes complicated and requires high skill

Engineering Contradiction:
Improvebiological safetyVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the metanephros from the embryo at an early stage (before immune system development) and performs all subsequent operations outside the living body. This separation eliminates the need for complex in vivo manipulations and high-skill embryonic injections, while maintaining biological safety through controlled ex vivo culture conditions.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The metanephros is harvested and prepared in advance during the immunologically tolerant period before the immune system develops. By performing the transplantation into the metanephros outside the body before immune rejection occurs, the process avoids complex immune management while ensuring biological safety.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If whole embryo culture is performed to obtain functional artificial kidney precursor, then the precursor can be obtained, but contamination risk increases and purification becomes complicated

Engineering Contradiction:
Improvefunctional capabilityVSAvoidcontamination risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The metanephros is extracted from the embryo and cultured separately outside the living body. This extraction eliminates the risk of contamination from the complex embryonic environment and surrounding tissues, while still allowing the metanephros to develop functional capabilities in a controlled ex vivo culture system.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the kidney development process by isolating only the metanephros portion from the entire embryo. This segmentation allows for simplified culture conditions, reduced contamination risk, and easier purification, while the metanephros retains its ability to develop into a functional artificial kidney precursor.

Inventive Principle:
Principle #1Segmentation

3Reliability

If mesenchymal stem cells are injected into the embryo during immune tolerance period, then the precursor can be obtained, but treatment schedule flexibility is reduced

Engineering Contradiction:
Improveimmune compatibilityVSAvoidschedule flexibility
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The metanephros is harvested and stored in advance during the immunologically tolerant period. This preliminary action allows the tissue to be prepared and preserved when immune compatibility is optimal, while enabling flexible scheduling of the actual transplantation procedure later without time constraints.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent separates the harvesting phase (during immune tolerance) from the transplantation phase. By segmenting these operations and using ex vivo culture and storage, the process achieves both immune compatibility and schedule flexibility, as the metanephros can be prepared in advance and transplanted when convenient.

Inventive Principle:
Principle #1Segmentation

4Reliability

If complex purification processes are performed after embryo cultivation, then the precursor can be obtained, but the overall process becomes more complicated

Engineering Contradiction:
Improvebiological safetyVSAvoidpurification complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The metanephros is extracted and cultured in a controlled ex vivo environment from the beginning, which prevents contamination that would require complex purification. This extraction approach maintains biological safety through controlled culture conditions while eliminating the need for complicated post-cultivation purification procedures.

Inventive Principle:
Principle #2Taking out (Extraction)

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 approach simplifies the production process, ensures biological safety, and eliminates the risk of contamination, enabling flexible treatment timing and efficient erythropoietin production when transplanted into a mammal, specifically addressing the limitations of existing methods by providing a safe and effective artificial kidney precursor.

Implementation Method 1

freezing a mammalian metanephros separated out from a living body

Methodology Applied
Scientific EffectFreezing: Freezing

Implementation Method 2

thawing the frozen mammalian metanephros

Methodology Applied
Scientific EffectThawing: Melting

Data Source

PatentUS9758766B2Artificial kidney precursor and process for production thereof
Publication Date: 2017.09.12 OTSUKA PHARMACEUTICAL FACTORY INC

AI summary

The present invention provides an artificial kidney precursor containing a non-human mammalian metanephros separated out from a living body, wherein the metanephros has been subjected to freezing and thawing treatments outside a living body, and contains mammalian mesenchymal stem cells transferred outside a living body, and a method of production thereof.