| University of Michigan Health System |
Scientists have coaxed stem cells to grow the first three-dimensional mini lungs. Previous research has focused on deriving lung tissue from flat cell systems or growing cells onto scaffolds made from donated organs.
In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.
In a study published in the online journal eLife the multi-institution team defined the system for generating the self-organizing human lung organoids, 3D structures that mimic the structure and complexity of human lungs.
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| Figure 1. Generation of three-dimensional ventral anterior foregut spheroids from endoderm monolayers.
(A)
hESCs were differentiated into foregut endoderm by treating cells with 4
days of Activin A (ACTA) followed by 4 days of NOG+SB. (B) Foregut endoderm (NOG+SB) had high expression of the foregut marker SOX2 while the hindgut marker CDX2
was significantly reduced compared to untreated endoderm controls
(End). NOG+SB monolayers had high expression of ventral anterior foregut
genes NKX2.1 and PAX8 while the posterior foregut marker PDX1 was reduced. The foregut marker HHEX is expressed in the developing liver, biliary system, and thyroid and remained unchanged. (C)
The majority of cells in NOG+SB treated cultures were SOX2 positive
(green) compared to the control, in which only scattered clusters of
cells were SOX2 positive. The scale bar represents 200 µm. (D)
hESCs were differentiated into foregut spheroids by treating cells with
4 days of ACTA and then additional 4–6 days of NOG+SB+FGF4+Ch.
Representative images of a spheroid in a matrigel droplet are shown as a
whole mount image. Scale bar represents 100 µm. (E) Foregut spheroids (NOG+SB+FGF4+Ch) had high expression of the foregut marker SOX2 while the hindgut marker CDX2
was significantly reduced compared to untreated endoderm control (End)
(top panel). Spheroids had high expression of anterior foregut genes NKX2.1 and PAX8 while the posterior foregut marker PDX1 was reduced and HHEX was unchanged (bottom panel). *p < 0.05, error bars represent SEM. (F)
The majority of cells in foregut spheroids are FOXA2+ (green, left
panel) and SOX2+ (white, right panel) and ECAD+ (red, right panel).
Scale bar represent 50 µm.
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