Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium

Beth A. Lindborg, John H. Brekke, Amanda L. Vegoe, Connor B. Ulrich, Kerri T. Haider, Sandhya Subramaniam, Scott L. Venhuizen, Cindy R. Eide, Paul J. Orchard, Weili Chen, Qi Wang, Francisco Pelaez, Carolyn M. Scott, Efrosini Kokkoli, Susan A. Keirstead, James R. Dutton, Jakub Tolar, Timothy D. O’Brien

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10–14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable.

Original languageEnglish (US)
Pages (from-to)970-979
Number of pages10
JournalStem Cells Translational Medicine
Volume5
Issue number7
DOIs
StatePublished - Jan 1 2016

Fingerprint

Organoids
Induced Pluripotent Stem Cells
Hydrogel
Culture Media
Cell Culture Techniques
Technology
Pluripotent Stem Cells
Precision Medicine
Rhombencephalon
Neural Tube
Prosencephalon
Mesencephalon
Reverse Transcription
Glutamic Acid
Gene Expression
Polymerase Chain Reaction
Proteins

Keywords

  • Adrenoleukodystrophy
  • Brain
  • In vitro techniques
  • Organoids
  • Stem cells

Cite this

Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. / Lindborg, Beth A.; Brekke, John H.; Vegoe, Amanda L.; Ulrich, Connor B.; Haider, Kerri T.; Subramaniam, Sandhya; Venhuizen, Scott L.; Eide, Cindy R.; Orchard, Paul J.; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M.; Kokkoli, Efrosini; Keirstead, Susan A.; Dutton, James R.; Tolar, Jakub; O’Brien, Timothy D.

In: Stem Cells Translational Medicine, Vol. 5, No. 7, 01.01.2016, p. 970-979.

Research output: Contribution to journalArticle

Lindborg, Beth A. ; Brekke, John H. ; Vegoe, Amanda L. ; Ulrich, Connor B. ; Haider, Kerri T. ; Subramaniam, Sandhya ; Venhuizen, Scott L. ; Eide, Cindy R. ; Orchard, Paul J. ; Chen, Weili ; Wang, Qi ; Pelaez, Francisco ; Scott, Carolyn M. ; Kokkoli, Efrosini ; Keirstead, Susan A. ; Dutton, James R. ; Tolar, Jakub ; O’Brien, Timothy D. / Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. In: Stem Cells Translational Medicine. 2016 ; Vol. 5, No. 7. pp. 970-979.
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