Amniotic Fluid Stem Cell Expansion of Immune Modulatory Cells

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Solution Overview

Problem

Current methods face challenges in effectively expanding immune regulator cells for treating ischemic neurological conditions.

Innovation Solution

The method involves obtaining an allogeneic amniotic fluid stem cell population, culturing it with autologous immune cells, and extracting cells with immune modulatory properties for use in treating inflammatory conditions, utilizing specific cell surface markers and culture conditions to maintain cell pluripotency and multipotency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods are used to expand immune regulator cells, then the treatment process is simple, but the expansion efficiency and effectiveness are insufficient

Engineering Contradiction:
Improveexpansion efficiency of immune regulator cellsVSAvoidcomplexity of cell culture system
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent introduces amniotic fluid stem cells as intermediary cells that mediate the expansion and differentiation of immune regulator cells. These stem cells provide a supportive microenvironment through cell-cell interactions and secreted factors, enabling efficient expansion of immune cells without requiring complex direct stimulation systems. The amniotic fluid stem cells act as a natural mediator that simplifies the overall culture system while dramatically improving expansion efficiency.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent utilizes specific culture parameters including defined media compositions, growth factors (such as IL-2, IL-7, IL-15), and physical conditions (temperature, pH, oxygen levels) to optimize the expansion of immune regulator cells. By precisely controlling these parameters and using amniotic fluid stem cells as a biological parameter, the system achieves high expansion efficiency while maintaining cellular functionality and reducing system complexity.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If immune regulator cells are expanded using traditional methods, then the procedure is straightforward, but the cells lack sufficient immune modulatory properties and durability

Engineering Contradiction:
Improvedurability and immortality of cultured cellsVSAvoidease of cell expansion process
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

Amniotic fluid stem cells serve as intermediary cells that confer durability and immortality properties to the cultured immune regulator cells. These stem cells provide long-term survival signals and protective microenvironments that enable the immune cells to maintain their functionality over extended periods. The intermediary interaction between amniotic fluid stem cells and immune cells transforms transient immune cells into durable, long-lasting therapeutic cells.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs preliminary conditioning of amniotic fluid stem cells before they are used to expand immune regulator cells. This preliminary action involves pre-treating the stem cells with specific growth factors and conditioning media to optimize their immunomodulatory capacity. By preparing the stem cells in advance with enhanced properties, the subsequent expansion process becomes more efficient and produces cells with superior durability and immune modulatory characteristics.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If autologous stem cells are used for immune modulation, then the treatment is personalized, but the cell population is limited and may not provide sufficient expansion capacity

Engineering Contradiction:
Improvequantity of immune modulatory cells availableVSAvoidversatility of cell differentiation
Core Design Contradiction:
Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent uses amniotic fluid stem cells as intermediary cells that can differentiate into multiple cell types, providing both quantity expansion and versatility. These stem cells serve as a universal platform that can generate various immune cell types (T cells, B cells, NK cells, macrophages) depending on the differentiation conditions. This intermediary approach allows a single stem cell source to provide diverse immune cell populations, greatly increasing the quantity and versatility available for treatment.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

Amniotic fluid stem cells possess universal properties that enable them to differentiate into multiple cell lineages and serve various functions. The patent exploits this multi-functionality by using the same stem cell population to generate different types of immune regulator cells tailored to specific therapeutic needs. This universal platform allows a single cell source to address multiple therapeutic requirements, providing both quantity expansion and functional versatility.

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

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 generates immortal, multipotent cells capable of differentiating into various cell types, effectively expanding immune modulatory cells for therapeutic use in neuroinflammatory conditions, demonstrating superior immune modulation and regenerative capabilities.

Implementation Method 1

The cells described in the invention are immortal in culture, maintain cuploidy for >1 year in culture, share markers with human ES cells, and are capable of differentiating into all three germ layers of the developing embryo, Endoderm, Mesoderm and Ectoderm

Methodology Applied
Scientific EffectCellular differentiation:

Implementation Method 2

amniotic stem cells are grown together with peripheral blood mononuclear cells in a culture containing a 1:1 ratio. Culture is performed for 7 days in the presence of IL-2 at 35 ng per ml

Methodology Applied
Scientific EffectCellular proliferation:

Data Source

PatentUS11795433B2Generation of autologous immune modulatory cells for treatment of neurological conditions
Publication Date: 2023.10.24 CREATIVE MEDICAL TECHNOLOGIES INC
  • US11795433B2 patent drawing

AI summary

Disclosed are means, methods, and compositions of matter useful for treatment of neuroinflammation, autoimmunity, transplant rejection, or graft versus host disease (GVHD) comprising exposing autologous immune cells to allogeneic amniotic fluid derived stem cells. In one embodiment peripheral blood mononuclear cells are cultured in the presence of amniotic fluid stem cells in the presence of interleukin-2 for a period of time sufficient to endow tolerogenic properties. Said tolerogenic properties include ability to suppress adaptive or innate immune responses. In another embodiment the invention provides methods of generating antigen specific immune regulatory cells by culture of lymphocytes together with amniotic fluid stem cells in the presence of antigen to which specific immune regulation is desired.