iPSC-Derived Myeloid Cell Production for Scalable Cell Therapy

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Solution Overview

Problem

The clinical use of innate myeloid lineage cells, such as monocytes, macrophages, and dendritic cells, is limited by their small numbers in regular leukapheresis products, hampering their application in therapies for inflammation, autoimmune diseases, and cancer.

Innovation Solution

A method is developed to generate hematopoietic lineages, including myeloid cells, from human induced pluripotent stem cells (iPSCs) through ex vivo processes, involving differentiation to embryoid bodies, CD34+ enrichment, endothelial-to-hematopoietic transition, and gene editing to overcome HLA matching issues, allowing for large-scale production of cells like monocytes, macrophages, and dendritic cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If innate myeloid lineage cells are isolated from regular leukapheresis products, then the cells can be obtained through a standard procedure, but the numbers of such cells are small and insufficient for clinical therapy

Engineering Contradiction:

Improvestandard isolation procedureVSAvoidnumber of myeloid cells

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by generating and expanding myeloid lineage cells ex vivo before clinical administration. Induced pluripotent stem cells (iPSCs) are differentiated into myeloid cells in advance, allowing sufficient cell numbers to be produced for therapy while maintaining the benefit of using a standardized differentiation protocol

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses iPSCs as a renewable source to copy and generate large numbers of myeloid cells. The iPSCs can be differentiated into myeloid lineage cells repeatedly, creating a scalable supply that overcomes the limitation of small cell numbers from leukapheresis while maintaining functional similarity to primary cells

Inventive Principle:

Principle #26Copying

2Productivity

If allogeneic myeloid cells are used for therapy, then cell availability is improved, but HLA matching issues and immune rejection risks arise

Engineering Contradiction:

Improvecell availabilityVSAvoidhistocompatibility

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent extracts and removes HLA antigens from the myeloid cells through gene editing. By deleting HLA class I and class II alleles, the cells become HLA-negative, eliminating the primary cause of immune rejection and allowing universal allogeneic transplantation without HLA matching requirements

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of HLA-mismatched allogeneic cells (immune rejection) into a benefit by creating HLA-negative cells. These edited cells can be used as universal donor cells for any patient, transforming the histocompatibility problem into a solution that enables broad applicability

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250368954A1Myeloid lineages derived from pluripotent cells

Publication Date: 2025.12.04 GARUDA THERAPEUTICS INC

AI summary

The present disclosure provides for efficient ex vivo processes for generating myeloid cell lineages from human induced pluripotent stem cells (iPSCs). Cells generated according to the disclosure in various embodiments are functional and/or more closely resemble the corresponding lineage isolated from peripheral blood, bone marrow, or other tissues. The present invention in some aspects provides isolated cells and cell compositions produced by the methods disclosed herein, as well as methods for cell therapy.