Human Facilitating Cells Enhance Stem Cell Engraftment

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Solution Overview

Problem

Current therapeutic protocols for hematopoietic stem cell transplantation face challenges in achieving long-term engraftment and immune system chimerism, often requiring harsh conditioning regimens and risking graft-versus-host disease.

Innovation Solution

The use of human facilitating cells (hFCs), specifically characterized by phenotypes such as CD8+ / alpha beta TCR- / CD56dim/neg and CD8+ / alpha beta TCR- / CD56bright, which are combined with hematopoietic stem cells (HSCs) to enhance engraftment and induce donor-specific tolerance, reducing the need for intense conditioning and minimizing graft-versus-host disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If harsh conditioning regimens are used to achieve long-term engraftment, then engraftment success is improved, but graft-versus-host disease risk increases

Engineering Contradiction:

Improveengraftment successVSAvoidgraft-versus-host disease risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces facilitating cells as intermediary cells that mediate between the transplanted stem cells and the recipient's immune system. These facilitating cells express specific surface markers (CD4+, CD8+, CD11c+, CD123+) and facilitate engraftment while inducing donor-specific tolerance, thereby reducing graft-versus-host disease risk without compromising engraftment success

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the cellular composition parameters of the transplant by including facilitating cells with specific phenotypic characteristics (CD4+, CD8+, CD11c+, CD123+ markers). This parameter change in cell population composition enables improved engraftment and immune tolerance without requiring harsh conditioning regimens

Inventive Principle:

Principle #35Parameter changes

2Duration of action of stationary object

If intense conditioning is applied to ensure engraftment, then engraftment durability is improved, but immune system damage worsens

Engineering Contradiction:

Improveengraftment durabilityVSAvoidimmune system damage

Core Design Contradiction:

Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary action by pre-conditioning the stem cell product with facilitating cells before transplantation. These facilitating cells are prepared in advance with specific surface marker expression patterns that enable them to facilitate engraftment and induce tolerance, reducing the need for intense post-transplantation conditioning

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Facilitating cells serve as intermediaries that protect the recipient's immune system from damage while ensuring durable engraftment. These cells express specific markers (CD4+, CD8+, CD11c+, CD123+) and mediate the interaction between donor stem cells and recipient immune system, inducing donor-specific tolerance without requiring intensive conditioning

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20230226115A1Human facilitating cells

Publication Date: 2023.07.20 UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION INC

AI summary

The present disclosure relates to human facilitating cells (hFC), and methods of isolating, characterizing, and using such hFCs.