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Decellularized Lung Extracellular Matrix Scaffold Promotes Human Embryonic Stem Cell Differentiation towards Alveolar

Afshin Noori^1,2, Mohammad Reza Mokhber Dezfouli^1,3, Sareh Rajabi^2,4

¹Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

|July 12, 2023

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Sheep lung decellularized extracellular matrix (dECM) scaffolds promote human embryonic stem cell differentiation into lung progenitor cells. This biomaterial enhances the development of alveolar epithelial cells, offering potential for lung regenerative medicine.

Area of Science:

Biomaterials Science
Stem Cell Biology
Regenerative Medicine

Background:

Efficient generation of functional alveolar epithelial cells is crucial for treating lung diseases.
Decellularized extracellular matrix (dECM) scaffolds retain native tissue properties and can guide stem cell differentiation.
Lung dECM offers a promising substrate for directing stem cell fate towards lung lineages.

Purpose of the Study:

To investigate the efficacy of sheep lung dECM-derived scaffolds in promoting the differentiation and maturation of human embryonic stem cell (hESC)-derived lung progenitor cells.
To compare the dECM scaffold with a dECM hydrogel and fibronectin-coated plates for their ability to induce lung progenitor cell development.

Main Methods:

Decellularization of sheep lungs to create dECM scaffolds and hydrogels.

Keywords:

Decellularization Differentiation Hydrogel Lung Scaffold

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Last Updated: Jul 23, 2025

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Characterization of dECM scaffolds for composition (collagen, glycosaminoglycans) and ultrastructure.

Comparison of dECM scaffold, dECM hydrogel, and fibronectin-coated plates for inducing differentiation of hESC-derived definitive endoderm (DE) into lung progenitor cells.

Assessment of differentiation using immunostaining and real-time PCR.

Main Results:

dECM scaffolds maintained native porous structures and biochemical composition without cellular material.
All tested conditions supported lung progenitor cell differentiation, indicated by NKX2.1, P63, and CK5 expression.
DE cells on dECM scaffolds and hydrogels showed increased SOX9 expression, a marker for distal airway epithelium.
dECM scaffolds significantly enhanced the expression of AT2 cell (SFTPC), ciliated cell (FOXJ1), and secretory cell (MUC5A) markers compared to other groups.

Conclusions:

Sheep lung dECM-derived scaffolds are superior to dECM hydrogels and fibronectin-coated plates in promoting the differentiation of definitive endoderm cells into lung alveolar progenitor cells.
dECM scaffolds provide a conducive microenvironment for guiding stem cell differentiation towards specific lung epithelial cell types.
These findings support the potential of dECM scaffolds as a therapeutic biomaterial for lung regenerative medicine.