Adipose tissue-derived ECM hydrogels as a 3D platform for neural differentiation and brain diseases

The interplay between the extracellular matrix and cells significantly impacts cellular survival, proliferation, and differentiation. Cell growth within 3D scaffolds, particularly hydrogels that mimic cellular microenvironments, offers more relevant insights into tissue development compared to traditional 2D systems. This study explores the behavior of neural stem cells and their differentiation within 3D pure adipose tissue-derived ECM (adECM) hydrogels. These hydrogels provide both physical and biochemical cues that closely resemble the 3D microarchitecture of native tissues. Encapsulating neuroectodermal NE-4C cells in adECM hydrogels at different concentrations revealed intriguing divergent cellular responses. While variations in fiber structure and pore formation between hydrogels did not significantly affect cell survival, they notably influenced the differentiation process. Analysis of neural-lineage-specific markers, such as TUBB3 and GFAP, demonstrated divergent differentiation outcomes. This biologically derived, tissue-specific 3D platform enables in vitro study of neural differentiation and lays the groundwork for future neural models relevant to regenerative medicine and neurodegenerative research. Originally published in Materials Advances (Royal Society of Chemistry, 2025) under the Creative Commons Attribution 3.0 Unported (CC BY 3.0) license. DOI of the original publication: 10.1039/d5ma00310e . Data availability: https://cloud.iesl.forth.gr/index.php/s/jzior2YScxwaxyt Funding: European Commission, Horizon 2020 – NFFA-Europe Pilot (Grant Agreement No. 101007417) European Commission, Horizon 2020 – FET Open, NeuroStimSpinal Project (Grant Agreement No. 829060)