Artificial Extracellular Matrix for Enhanced Maturation of Human iPSCs-derived Neurons

Artificial Extracellular Matrix for Enhanced Maturation of Human iPSCs-derived Neurons

NU 2018-157

Peptide amphiphile nanofibers enhance neuron maturation by promoting high mobility while reducing cell aggregation.

INVENTORS

Samuel I. Stupp*

Zaida Alvarez Pinto

Juan Alberto Ortega Cano

Kohei Sato

Evangelos Kiskinis

SHORT DESCRIPTION

A dynamic artificial extracellular matrix (ECM) composed of a laminin-mimetic peptide amphiphile can enhance the functional maturation of human induced pluripotent stem cells (hiPSCs)-derived neurons while reducing neuronal aggregation.

BACKGROUND

Human-induced pluripotent stem cells (hiPSCs) are widely used to study human development and diseases, screen drugs, and develop cell therapies. However, they face challenges such as abnormal cell clustering and poor neuron maturation, partly due to the lack of effective supportive extracellular matrix (ECM). Commercial ECM coatings and matrices, such as laminin, Matrigel, and fibronectin, allow neuron attachment but lack the dynamic molecular properties needed for proper neuronal maturation and tend to form large clusters. While glial cell co-culture systems can improve maturation, they are costly and exhibit batch-to-batch variability. These limitations necessitate the development of a more effective ECM-mimetic matrix.

ABSTRACT

Northwestern researchers have developed IKVAV-PA2, a peptide amphiphile that self-assembles into supramolecular nanofibers and mimics the dynamic properties of the natural ECM. It features a bioactive IKVAV peptide for neuron attachment and a mobile non-bioactive domain for matrix dynamics. Compared to glial cells co-culture and commercial matrices, IKVAV-PA2, with enhanced internal supramolecular motion, enables a homogeneous cellular distribution, promotes functional maturation, and offers greater long-term stability of hiPSC-derived motor and cortical neurons. Its chemically defined composition minimizes batch-to-batch variability and offers a more cost-effective alternative.

APPLICATIONS

• Long-term culture and maturation of stem-cell-derived neurons in vitro
• ECM-mimetic platform for neurodegenerative, neurodevelopmental, and neurological diseases.

INVO CONTACT

invo@northwestern.edu