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)

Divya Varun, Gayathri Rajaram Srinivasan, Yi Huan Tsai, Hyun Je Kim, Joshua Cutts, Francis Petty, Ryan Merkley, Nicholas Stephanopoulos, Dasa Dolezalova, Martin Marsala, David Brafman

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)120-130
Number of pages11
JournalActa Biomaterialia
Volume48
DOIs
StatePublished - Jan 15 2017

Keywords

  • Defined conditions
  • Human neural progenitor cells
  • Human pluripotent stem cells
  • Peptide

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering
  • Molecular Biology

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