Bioprinting and Differentiation of Adipose-Derived Stromal Cell Spheroids for a 3D Breast Cancer-Adipose Tissue Model

Cells

Ali Nadernezhad¹  Jürgen Groll¹  Johannes Herbig¹  Jörg Teßmar¹  Süleyman Ergün²  Ben Fabry³  Nadine Grummel³  Hannes Horder⁴  Torsten Blunk⁴  Petra Bauer-Kreisel⁴  Mar Guaza Lasheras⁴ 

[1] Chair for Functional Materials in Medicine and Dentistry, Bavarian Polymer Institute, University of Würzburg, 97080 Würzburg, Germany;Department of Medicine, Institute of Anatomy and Cell Biology, University of Würzburg, 97070 Würzburg, Germany;Department of Physics, Friedrich-Alexander University Erlangen-Nürnberg, 91052 Erlangen, Germany;Department of Trauma, Hand, Plastic and Reconstructive Surgery, University of Würzburg, 97080 Würzburg, Germany;

关键词: adipose-derived stromal cells;    adipose tissue;    bioprinting;    breast cancer model;    extracellular matrix;    hyaluronic acid;   

DOI  :  10.3390/cells10040803

来源: DOAJ

【 摘 要 】

Biofabrication, including printing technologies, has emerged as a powerful approach to the design of disease models, such as in cancer research. In breast cancer, adipose tissue has been acknowledged as an important part of the tumor microenvironment favoring tumor progression. Therefore, in this study, a 3D-printed breast cancer model for facilitating investigations into cancer cell-adipocyte interaction was developed. First, we focused on the printability of human adipose-derived stromal cell (ASC) spheroids in an extrusion-based bioprinting setup and the adipogenic differentiation within printed spheroids into adipose microtissues. The printing process was optimized in terms of spheroid viability and homogeneous spheroid distribution in a hyaluronic acid-based bioink. Adipogenic differentiation after printing was demonstrated by lipid accumulation, expression of adipogenic marker genes, and an adipogenic ECM profile. Subsequently, a breast cancer cell (MDA-MB-231) compartment was printed onto the adipose tissue constructs. After nine days of co-culture, we observed a cancer cell-induced reduction of the lipid content and a remodeling of the ECM within the adipose tissues, with increased fibronectin, collagen I and collagen VI expression. Together, our data demonstrate that 3D-printed breast cancer-adipose tissue models can recapitulate important aspects of the complex cell–cell and cell–matrix interplay within the tumor-stroma microenvironment.

【 授权许可】

Unknown