Generation of Functional Human Retinal Ganglion Cells with Target Specificity from Pluripotent Stem Cells by Chemically Defined Recapitulation of Developmental Mechanism

Pooja Teotia, Divyan A. Chopra, Shashank Manohar Dravid, Matthew J. Van Hook, Fang Qiu, John Morrison, Angie Rizzino, Iqbal Ahmad

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) lead to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, that is, the embryonic stem cells and induced pluripotent stem cells. Here, we demonstrate a rapid and safe, stage-specific, chemically defined protocol that selectively generates RGCs across species, including human, by recapitulating the developmental mechanism. The de novo generated RGCs from pluripotent cells are similar to native RGCs at the molecular, biochemical, functional levels. They also express axon guidance molecules, and discriminate between specific and nonspecific targets, and are nontumorigenic.

Original languageEnglish (US)
JournalStem Cells
DOIs
StateAccepted/In press - 2016

Keywords

  • Chemically defined medium
  • Directed differentiation
  • Embryonic stem cells
  • Glaucoma
  • Induced pluripotent stem cells
  • Retinal ganglion cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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