A Biomimetic, Stem Cell-Derived In Vitro Ocular Outflow Model

Adv Biosyst. 2020 Sep;4(9):e2000004. doi: 10.1002/adbi.202000004. Epub 2020 Jul 30.

Abstract

Age-related human trabecular meshwork (HTM) cell loss is suggested to affect its ability to regulate aqueous humor outflow in the eye. In addition, disease-related HTM cell loss is suggested to lead to elevated intraocular pressure in glaucoma. Induced pluripotent stem cell (iPSC)-derived trabecular meshwork (TM) cells are promising autologous cell sources that can be used to restore the declining TM cell population and function. Previously, an in vitro HTM model is bioengineered for understanding HTM cell biology and screening of pharmacological or biological agents that affect trabecular outflow facility. In this study, it is demonstrated that human iPSC-derived TM cells cultured on SU-8 scaffolds exhibit HTM-like cell morphology, extracellular matrix deposition, and drug responsiveness to dexamethasone treatment. These findings suggest that iPSC-derived TM cells behave like primary HTM cells and can thus serve as reproducible and scalable cell sources when using this in vitro system for glaucoma drug screening and further understanding of outflow pathway physiology, leading to personalized medicine.

Keywords: 3D culture; glaucoma; microfabrication; outflow; stem cell; trabecular meshwork.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomimetics
  • Cell Culture Techniques / methods
  • Glaucoma / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Models, Biological*
  • Trabecular Meshwork* / cytology
  • Trabecular Meshwork* / metabolism