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2016 ; 5
(7
): 970-9
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gab.com Text
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Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells
Using a Chemically Defined Hydrogel and Defined Cell Culture Medium
#MMPMID27177577
Lindborg BA
; Brekke JH
; Vegoe AL
; Ulrich CB
; Haider KT
; Subramaniam S
; Venhuizen SL
; Eide CR
; Orchard PJ
; Chen W
; Wang Q
; Pelaez F
; Scott CM
; Kokkoli E
; Keirstead SA
; Dutton JR
; Tolar J
; O'Brien TD
Stem Cells Transl Med
2016[Jul]; 5
(7
): 970-9
PMID27177577
show ga
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. SIGNIFICANCE: Tissue organoids are a
promising technology with many potential applications, such as pharmaceutical
screens and development of in vitro disease models, particularly for human
polygenic conditions where animal models are insufficient. This work describes a
robust and simple method for generating cerebral organoids from human induced
pluripotent stem cells by using a chemically defined hydrogel material and
chemically defined culture medium. This method, by virtue of its simplicity and
use of defined materials, greatly facilitates access to cerebral organoid
technology, enables scalable applications, and provides a potential pathway to
translational applications where defined components are desirable.