title: A robust vitronectin-derived peptide for the scalable long-term expansion and neuronal differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (hNPCs).
abstract: Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged neurons and supporting cells of the central nervous system (CNS) are of great therapeutic interest. To that end, human pluripotent stem cell (hPSC) derived neural progenitor cells (hNPCs) and their neuronal derivatives could provide the cellular 'raw material' needed for regenerative medicine therapies for a variety of CNS disorders. In addition, hNPCs derived from patient-specific hPSCs could be used to elucidate the underlying mechanisms of neurodegenerative diseases and identify potential drug candidates. However, the scientific and clinical application of hNPCs requires the development of robust, defined, and scalable substrates for their long-term expansion and neuronal differentiation. In this study, we rationally designed a vitronectin-derived peptide (VDP) that served as an adhesive growth substrate for the long-term expansion of several hNPC lines. Moreover, VDP-coated surfaces allowed for the directed neuronal differentiation of hNPC at levels similar to cells differentiated on traditional extracellular matrix protein-based substrates. Overall, the ability of VDP to support the long-term expansion and directed neuronal differentiation of hNPCs will significantly advance the future translational application of these cells in treating injuries, disorders, and diseases of the CNS.
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Divya
authors.initials: D
authors.lastname: Varun
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Gayathri Rajaram
authors.initials: GR
authors.lastname: Srinivasan
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Yi-Huan
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Hyun-Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Cutts
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States.
authors.forename: Francis
authors.initials: F
authors.lastname: Petty
authors.affiliation: School of Molecular Sciences and Biodesign Institute Center for Molecular Design and Biomimetics, Arizona State University, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Merkley
authors.affiliation: School of Molecular Sciences and Biodesign Institute Center for Molecular Design and Biomimetics, Arizona State University, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stephanopoulos
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Dasa
authors.initials: D
authors.lastname: Dolezalova
authors.affiliation: Department of Anesthesiology, University of California - San Diego, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, United States. Electronic address: david.brafman@asu.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Brafman
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019096:Vitronectin / Q000494:pharmacology*
chemical_list: D015815:Cell Adhesion Molecules; D020099:Coated Materials, Biocompatible; D016326:Extracellular Matrix Proteins; D010455:Peptides; D019096:Vitronectin
keywords: Defined conditions; Human neural progenitor cells; Human pluripotent stem cells; Peptide