Cancer Stem Cell Culture in Simulated Microgravity Bioreactor

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Solution Overview

Problem

Current methods for culturing stem cells, particularly cancer stem cells, face challenges in maintaining their undifferentiated state and sensitivity to chemotherapeutic agents, leading to limited effectiveness in cancer treatment due to resistance and regrowth issues.

Innovation Solution

Culturing cancer stem cells in a horizontally rotating, fluid-filled bioreactor with a membrane for gas exchange, simulating microgravity conditions, which increases telomerase activity, telomere length, and susceptibility to chemotherapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are cultured under normal gravity conditions, then they can be maintained in undifferentiated state, but they develop resistance to chemotherapeutic agents and show limited effectiveness in cancer treatment

Engineering Contradiction:
Improveeffectiveness in cancer treatmentVSAvoidresistance to chemotherapeutic agents
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical parameter of gravity from normal Earth gravity to simulated microgravity conditions using a rotating bioreactor. This parameter change fundamentally alters the cellular environment, causing cancer stem cells to maintain undifferentiated states while increasing their susceptibility to chemotherapeutic agents, thereby resolving the contradiction between maintaining stem cell properties and achieving treatment effectiveness

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If cancer stem cells are cultured to increase their population, then more cells are available for treatment, but their undifferentiated state is lost and they become more resistant to chemotherapy

Engineering Contradiction:
Improvenumber of stem cellsVSAvoidsusceptibility to chemotherapeutic agents
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent applies simulated microgravity conditions in a rotating bioreactor to culture cancer stem cells. This physical parameter change enables the simultaneous expansion of cell population and maintenance of undifferentiated state with increased chemotherapy susceptibility, resolving the contradiction between quantity production and treatment susceptibility

Inventive Principle:
Principle #35Parameter changes

3Productivity

If stem cells are cultured in conventional bioreactors with impeller stirring, then mixing and gas exchange are improved, but shear forces disrupt cell aggregation and tissue formation

Engineering Contradiction:
Improvecell culture efficiencyVSAvoidcell aggregation and tissue structure
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent replaces the mechanical impeller stirring system with a rotation-based system that simulates microgravity. This substitution eliminates high shear forces while maintaining effective mixing and gas exchange through rotational convection, thereby preserving cell aggregation and tissue structure while keeping culture efficiency high

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

Solution Approach 2:

The patent uses fluid dynamics and hydrodynamic focusing principles in the rotating bioreactor to achieve cell suspension and mixing without mechanical stirring. The rotational motion creates fluid flow patterns that uniformly distribute cells and nutrients while minimizing shear stresses, maintaining tissue construct integrity

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 enhances the life span of cancer stem cells, maintains their undifferentiated state, and increases their sensitivity to chemotherapy, potentially improving cancer treatment outcomes.

Implementation Method 1

The present invention relates to methods for culturing cancer stem cells in modeled microgravity conditions

Methodology Applied
Scientific EffectMicrogravity: Weightlessness

Implementation Method 2

a membrane for diffusion gas exchange to optimize gas/oxygen-supply

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2265708B1Methods for stem cell production and therapy
Publication Date: 2016.05.11 MARSHALL UNIVERSITY RESEARCH CORP
  • EP2265708B1 patent drawingFigure 1
  • EP2265708B1 patent drawingFigure 2
  • EP2265708B1 patent drawingFigure 3

AI summary

The present invention relates to methods for rapidly expanding a stem cell population with or without culture supplements in simulated micro gravity conditions. The present invention relates to methods for rapidly increasing the life span of stem cell populations without culture supplements in simulated microgravity conditions. The present invention also relates to methods for increasing the sensitivity of cancer stem cells to chemo therapeutic agents by culturing the cancer stem cells under microgravity conditions and in the presence of omega-3 fatty acids. The methods of the present invention can also be used to proliferate cancer cells by culturing them in the presence of omega-3 fatty acids. The present invention also relates to methods for testing the sensitivity of cancer cells and cancer stem cells to chemotherapeutic agents by culturing the cancer cells and cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce tissue for use in transplantation by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors by culturing stem cells or cancer stem cells under microgravity conditions. The methods of the present invention can also be used to produce cellular factors and growth factors to promote differentiation of cancer stem cells under microgravity conditions.