Umbilical Cord Lining Stem Cell Expansion via Fibronectin Substrate

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Solution Overview

Problem

Current methods for isolating and culturing umbilical cord lining stem cells (ULSCs) are inefficient in obtaining therapeutically relevant numbers and lack effective methods for differentiation and preservation for regenerative medicine applications.

Innovation Solution

A method involving the isolation of ULSCs from the umbilical cord lining using a fibronectin-coated substrate with a specific growth medium containing fetal bovine serum, growth factors, and antibiotics, allowing for adherence, expansion, and differentiation into various cell types, along with cryopreservation for long-term storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to isolate umbilical cord lining stem cells, then the isolation process is simple, but the efficiency of obtaining therapeutically relevant numbers is low

Engineering Contradiction:
Improveefficiency of obtaining therapeutically relevant numbersVSAvoidcomplexity of isolation and culturing methods
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies parameter changes by optimizing culture medium composition (including specific growth factors like bFGF, LIF, and EGF), adjusting serum concentration (10-20%), and modifying incubation conditions to enhance cell proliferation and achieve therapeutically relevant numbers efficiently

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses fibronectin-coated substrates as an intermediary to facilitate cell adherence and expansion, and employs cryopreservation techniques as an intermediary method to enable long-term storage and future therapeutic applications

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If conventional methods are used, then the isolation process is straightforward, but the ability to differentiate into various cell types is limited

Engineering Contradiction:
Improvedifferentiation capability into various cell typesVSAvoidease of isolation process
Core Design Contradiction:
Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent demonstrates multi-functionality by showing that the isolated ULSCs can differentiate into multiple cell types including adipogenic, osteogenic, chondrogenic, neurogenic, and cardiogenic cells, making them universally applicable for various regenerative medicine applications

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes parameter changes by adjusting culture medium composition and growth factors to direct ULSC differentiation toward specific lineages, enabling versatile tissue regeneration while maintaining a relatively simple isolation process

Inventive Principle:
Principle #35Parameter changes

3Loss of time

If conventional methods are used, then cell expansion is slow, but the time required to reach therapeutically relevant numbers is excessive

Engineering Contradiction:
Improvetime required to expand to therapeutically relevant numbersVSAvoidcell expansion rate
Core Design Contradiction:
Loss of timeVSProductivity

Solution Approach 1:

The patent applies parameter changes by optimizing culture conditions including growth factor concentrations (bFGF, LIF, EGF), serum levels (10-20%), and medium composition to dramatically enhance cell proliferation rates and reduce expansion time to therapeutically relevant numbers

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent ensures continuous cell expansion through sustained culture in optimized medium, regular passage, and maintained growth factor supplementation, enabling continuous production of therapeutically relevant cell numbers without interruption

Inventive Principle:
Principle #20Continuity of useful action

4Reliability

If conventional methods are used, then cell preservation is not effective, but long-term storage for future use is required

Engineering Contradiction:
Improveeffectiveness of cryopreservationVSAvoidcomplexity of preservation methods
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies phase transitions by using cryopreservation technology to transition ULSCs from a living state to a frozen state for long-term storage, and subsequently thawing and reviving them for future therapeutic applications, ensuring reliability while managing complexity

Inventive Principle:
Principle #36Phase transitions

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

ULSCs can be easily obtained and expanded to therapeutically relevant numbers, demonstrating broad plasticity and ability to differentiate into adipogenic, osteogenic, chondrogenic, neurogenic, and cardiogenic cells, and can be cryopreserved for future therapeutic use.

Implementation Method 1

culturing explants of the lining on a fibronectin-coated solid substrate in the presence of a low glucose growth medium for a period of time sufficient for the ULSCs to adhere to the fibronectin-coated solid substrate

Methodology Applied
Scientific EffectAdherence: Adhesive

Implementation Method 2

ULSCs can be propagated for at least 60 population doublings

Methodology Applied
Scientific EffectCell proliferation:

Implementation Method 3

ULSCs can be cryopreserved, making the cells suitable for banking of the cells for later therapeutic uses

Methodology Applied
Scientific EffectCryopreservation: Freezing

Data Source

PatentEP2483392B1Umbilical cord lining stem cells and methods and material for isolating and culturing same
Publication Date: 2015.11.11 DAVINCI BIOSCIENCES LLC
  • EP2483392B1 patent drawingFigure 1
  • EP2483392B1 patent drawingFigure 1
  • EP2483392B1 patent drawingFigure 2

AI summary

Human umbilical cord lining stem cells that are capable of differentiating into cells of the mesodermal lineage and ectodermal lineage are described, as well as methods of isolating, expanding, culturing, and cryopreserving such cells.