Ex Host Maturation of Germline Stem Cells for Tumor-Free Fertility Restoration

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Solution Overview

Problem

Current methods for preserving fertility in patients undergoing chemotherapy or radiation therapy are invasive and do not effectively prevent the reintroduction of tumor cells, and there are limited options for restoring fertility in individuals who have experienced germ cell depletion, particularly in prepubertal males and females.

Innovation Solution

A method for ex host maturation of immature germline stem cells into functional sperm or eggs using artificial seminiferous tubules and granulosa cells, respectively, under conditions mimicking in vivo maturation, allowing for cryopreservation and subsequent in vitro fertilization to avoid tumor contamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If direct re-implantation or autologous transplantation of germline stem cells is performed, then fertility restoration is achieved, but there is risk of re-introducing tumor cells contaminating the original explanted tissue

Engineering Contradiction:
Improvefertility restoration safetyVSAvoidtumor cell re-introduction risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts only the germline stem cells from the original testicular or ovarian tissue, separating them from any potential tumor cells. The isolated stem cells are then cultured and differentiated in vitro to produce mature sperm or eggs, which are used for reproduction without re-introducing the original tissue that may contain tumor contaminants.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses an intermediary in vitro culture and differentiation system to transform germline stem cells into mature reproductive cells. This intermediary process allows for controlled maturation outside the body, enabling fertility restoration while avoiding direct re-implantation of original tissue that could contain tumor cells.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If germline stem cells are cryopreserved and later re-implanted, then fertility can be restored, but the process is invasive and carries medical risks

Engineering Contradiction:
Improvefertility preservation effectivenessVSAvoidinvasiveness of procedure
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical surgical re-implantation process with an in vitro differentiation and maturation system. Instead of surgically re-inserting cryopreserved tissue or cells into the body, the stem cells are cultured and differentiated in controlled laboratory conditions to produce mature sperm or eggs that can be used for reproduction through less invasive means.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If chemotherapy or radiation therapy is administered to treat malignancies, then cancer is treated, but germline stem cells are depleted causing infertility

Engineering Contradiction:
Improvecancer treatment effectivenessVSAvoidgerm cell depletion
Core Design Contradiction:
ReliabilityVSLoss of substance

Solution Approach 1:

The patent performs preliminary cryopreservation of germline stem cells before chemotherapy or radiation therapy depletes them. By storing these stem cells in advance, the patent ensures a reservoir of germ cells that can later be differentiated and used for fertility restoration after the patient completes cancer treatment.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the state of germline stem cells from their native in vivo environment to cryopreserved storage conditions, and later to differentiated in vitro conditions. This parameter transformation allows the cells to survive chemotherapy and radiation that would otherwise destroy them, enabling future fertility restoration.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS9657267B2Ex host maturation of germline stem cells
Publication Date: 2017.05.23 HARVARDIANAMD CONSULTING
  • US9657267B2 patent drawing
  • US9657267B2 patent drawing
  • US9657267B2 patent drawing

AI summary

Methods are provided for the ex host maturation of immature germline cells into haploid gametes for restoration of fertility in patients in need thereof.