Wisconsin Alumni Research Foundation

Pluripotent Stem Cells
Pluripotent Stem Cells
Generating Hindbrain and Spinal Cord Cells from Human Stem Cells
WARF: P130353US03

Inventors: Randolph Ashton, Ethan Lippmann

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a method for deriving various types of neural cells found at different positions along the hindbrain and spinal cord.
Overview
While researchers have made great progress in differentiating human pluripotent stem cells (hPSCs) to neural cells of the anterior central nervous system (e.g., the midbrain and forebrain), efforts focusing on the hindbrain and spinal cord have met with little success.

It is known that during development a family of 39 HOX genes plays an important role in defining a neural cell’s positional identity within the rostral (top/front of the hindbrain) and caudal (bottom/tail end of the spinal cord) axis. Accordingly, a new method to derive neural cells such as neurons and astrocytes with specific rostral-caudal positional identity (i.e., having a detailed and predictable HOX gene expression profile) would be of great utility to researchers.
The Invention
UW–Madison researchers have developed a culture medium for producing neural cell populations (caudal lateral epiblasts, posterior neuroectoderm, posterior neuroepithelial cells or motor neurons) with desired positional identity within the hindbrain or spinal cord. This identity can be predicted a priori in a fully defined and scalable way based on HOX gene expression.

The culture medium is composed of standard ingredients and includes a fibroblast growth factor and an activator of β-catenin pathway signaling.
Applications
  • Disease modeling, regenerative therapy and drug screening
  • Current clinical trials are demonstrating the safety of transplanting analogous fetal tissues into the spinal cord as a regenerative therapy.
Key Benefits
  • Produces patient-specific cells with precise positional patterning along the hindbrain-spinal axis
  • Detailed and predictable HOX expression profiles
  • Fully defined, controllable and scalable
  • Could become the go-to technique for generating neural stem cells that can generate any cell found in the hindbrain and spinal cord with defined positional identity
  • No comparable method exists.
Stage of Development
The researchers have used their new method to differentiate neuroectoderm to hindbrain and spinal cord fate, and have determined the requirements for halting the differentiation process at a fixed positional location.
Additional Information
For More Information About the Inventors
Publications
  • Lippmann E.S., Williams C.E., Ruhl D.A., Estevez-Silva M.C., Chapman E.R., Coon J.J. and Ashton R.S. 2015. Deterministic HOX Patterning in Human Pluripotent Stem Cell-Derived Neuroectoderm. Stem Cell Reports. [Epub ahead of print]
  • Feldman E. L. et al. 2014. Intraspinal Neural Stem Cell Transplantation in Amyotrophic Lateral Sclerosis: Phase 1 Trial Outcomes. Annals of Neurology 75, 363–373.
For current licensing status, please contact Andy DeTienne at [javascript protected email address] or 608-960-9857

WARF