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by Keyword: Stemness
Blanco-Fernandez, Barbara, Bagci, Gulsun, Perez-Amodio, Soledad, Rey-Vinolas, Sergi, Ximenes-Carballo, Celia, Gato-Diaz, Uxia, Concheiro, Angel, Alvarez-Lorenzo, Carmen, Engel, Elisabeth, (2025). A bioprinted breast cancer model using bioinks of decellularized breast tissue for studying cancer stemness, invasion, and drug efficacy Acta Biomaterialia 203, 306-321 
Breast cancer 3D in vitro systems that replicate key tumor characteristics could assist drug discovery by providing more clinically translational models. Breast tumors are formed by hierarchically organized cancer and stromal cells and the extracellular matrix, all of which contribute to the disease progression and treatment response. 3D-bioprinting has enabled the creation of anatomically relevant constructs that better recapitulate the tumor architecture. The extracellular matrix's role in the tumor outcome has motivated the development of biomimetic bioinks. Among them, bioinks based on decellularized mammary glands can mimic many native biological cues. This work aims to develop a bioprinted 3D in vitro model of breast cancer using a biomimetic bioink based on decellularized mammary glands, and to investigate the effect of this bioink on the malignancy and drug resistance of breast cancer cells. The biomimetic bioink supported cell stemness, invasion, and an immunosuppressive environment but did not promote drug resistance. We also tested the effect of supplementing the bioink with collagen I, which is highly expressed in breast cancer, on breast cancer cells. We observed a higher expression of malignancy markers (COL1A1) and invasion markers (CDH2, MMP2). Next, we bioprinted a cancer model using human adipose mesenchymal stem cells and breast cancer cells to replicate tumor anatomy. These bioprinted models exhibited enhanced resistance to doxorubicin, particularly in the case of the bioink supplemented with collagen I. Therefore, supplementing the bioink with collagen I can promote the creation of more relevant cancer models for drug screening.
JTD Keywords: Bioink, Bioprinting, Breast cancer, Decellularized mammary gland, Invasiveness, Stemness
Villasante, A, Godier-Furnemont, A, Hernandez-Barranco, A, Le Coq, J, Boskovic, J, Peinado, H, Mora, J, Samitier, J, Vunjak-Novakovic, G, (2021). Horizontal transfer of the stemness-related markers EZH2 and GLI1 by neuroblastoma-derived extracellular vesicles in stromal cells Translational Research 237, 82-97
Neuroblastoma (NB) is the most common extracranial pediatric solid cancer originating from undifferentiated neural crest cells. NB cells express EZH2 and GLI1 genes that are known to maintain the undifferentiated phenotype of cancer stem cells (CSC) in NB. Recent studies suggest that tumor-derived extracellular vesicles (EVs) can regulate the transformation of surrounding cells into CSC by transferring tumor-specific molecules they contain. However, the horizontal transfer of EVs molecules in NB remains largely unknown. We report the analysis of NB-derived EVs in bioengineered models of NB that are based on a collagen 1/hyaluronic acid scaffold designed to mimic the native tumor niche. Using these models, we observed an enrichment of GLI1 and EZH2 mRNAs in NB-derived EVs. As a consequence of the uptake of NB-derived EVs, the host cells increased the expression levels of GLI1 and EZH2. These results suggest the alteration of the expression profile of stromal cells through an EV-based mechanism, and point the GLI1 and EZH2 mRNAs in the EV cargo as diagnostic biomarkers in NB.
JTD Keywords: exosomes, genes, lines, maintenance, pathway, proliferation, rna, stemness, tumor, Cancer
