Microbead-Based System for Production of Immune Cells from Stem Cells

Introduction

Differentiating stem cells into T cells is extremely challenging, and only relied on co-culture with thymus, the site of natural T cell differentiation, until a couple years ago. Recently stromal (development-supporting) cells, stably transduced with notch ligands (signal for differentiation), have been shown to be effective for committing stem cells to T cells. But these methods are not high throughput and can be difficult to translate into large scale production of therapeutic cells. Current systems rely on cell lines that are stably transfected with DLL1 (a similar notch ligand) but suffer from the mixing of cell types which complicates future cell isolation. Such transfected cell systems are complicated and translating them to large scale therapeutic cell production would be difficult.

Invention Description

This technology is the development of a novel, simple system for differentiating stem cells into T cells using particle-immobilized notch ligands and physically isolated stromal cells. The presence of the immobilized ligand on microbeads and the separate stromal layer provide the necessary signals to commit the stem cells to the T cell lineage. The novelty in the system lies in both the novel specific notch ligand and its presentation method for differentiating stem cells to the T cell lineage. Stem cells are cultured in inserts that separate the stromal cell population from the stem cell population. The microbeads independently present the notch signal to the stem cells and can be readily removed from the stem cell culture leaving a pure T cell population suitable for transplantation.

Benefits

• Ability for large scale therapeutic cell production
• Increases purity of differentiation of stem cells to T cells
• Much simpler technique than existing technologies
• Minimizes immunological concerns with animal/human cell co-cultures
• Eliminates mixing of cell types
• Feasible transplantation applications

Features

• Separation between supportive (stromal) cell and stem cell
• Novel notch ligand, DLL4, previously not studied
• Artificial environment synthesis of T cells from stem cells
• Immunoisolation between human/animal cell co-cultures used for T cell synthesis
• Microbead technology can be used for alternative cell phenotypes

Market Potential/Applications

This technology provides information on hematopoiesis--the formation of blood cells in the body and notch signaling--the pathway involved with cellular differentiation. This microbead method can be expanded to promote stem cell differentiation into other cell lineages beyond just T cells. This technology also provides a system that can be used to produce specific T cells, which activate immune response and identify foreign antigens, in an artificial environment for a variety of diseases such as HIV, leukemia, etc. This technology is a beneficial tool for human stem cell research.

IP Status

One U.S. Patent Application filed

UT Researcher

Krishnendu Roy, Ph.D., Department of Biomedical Engineering, The University of Texas at Austin

For further information please contact

University of Texas,
Austin, USA
Website : www.otc.utexas.edu