In pursuit of authenticity: Induced pluripotent stem cell-derived retinal pigment epithelium for clinical applications

Kiyoharu J. Miyagishima, Qin Wan, Barbara Corneo, Ruchi Sharma, Mostafa R. Lotfi, Nathan C. Boles, Fang Hua, Arvydas Maminishkis, Congxiao Zhang, Timothy Blenkinsop, Vladimir Khristov, Balendu S. Jha, Omar S. Memon, Sunita D’Souza, Sally Temple, Sheldon S. Miller, Kapil Bharti

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Induced pluripotent stem cells (iPSCs) can be efficiently differentiated into retinal pigment epithelium (RPE), offering the possibility of autologous cell replacement therapy for retinal degeneration stemming from RPE loss. The generation and maintenance of epithelial apical-basolateral polarity is fundamental for iPSC-derived RPE (iPSC-RPE) to recapitulate native RPE structure and function. Presently, no criteria have been established to determine clonal or donor based heterogeneity in the polarization and maturation state of iPSC-RPE. We provide an unbiased structural, molecular, and physiological evaluation of 15 iPSC-RPE that have been derived from distinct tissues from several different donors. We assessed the intact RPE monolayer in terms of an ATP-dependent signaling pathway that drives critical aspects of RPE function, including calcium and electrophysiological responses, as well as steady-state fluid transport. These responses have key in vivo counterparts that together help determine the homeostasis of the distal retina.Wecharacterized the donor and clonal variation and found that iPSC-RPE function was more significantly affected by the genetic differences between different donors than the epigenetic differences associated with different starting tissues. This study provides a reference dataset to authenticate genetically diverse iPSC-RPE derived for clinical applications.

Original languageEnglish
Pages (from-to)1562-1574
Number of pages13
JournalStem cells translational medicine
Volume5
Issue number11
DOIs
StatePublished - 1 Nov 2016

Keywords

  • Cell authentication
  • Cellular therapy
  • Genetic differences
  • Induced pluripotent stem cell (iPSC)
  • Retinal pigment epithelium

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