TY - JOUR A1 - Horder, Hannes A1 - Guaza Lasheras, Mar A1 - Grummel, Nadine A1 - Nadernezhad, Ali A1 - Herbig, Johannes A1 - Ergün, Süleyman A1 - Teßmar, Jörg A1 - Groll, Jürgen A1 - Fabry, Ben A1 - Bauer-Kreisel, Petra A1 - Blunk, Torsten T1 - Bioprinting and differentiation of adipose-derived stromal cell spheroids for a 3D breast cancer-adipose tissue model JF - Cells N2 - 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 KW - adipose-derived stromal cells KW - adipose tissue KW - bioprinting KW - breast cancer model KW - extracellular matrix KW - hyaluronic acid KW - spheroids Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236496 VL - 10 IS - 4 ER - TY - JOUR A1 - Bachmann, Julia A1 - Ehlert, Elias A1 - Becker, Matthias A1 - Otto, Christoph A1 - Radeloff, Katrin A1 - Blunk, Torsten A1 - Bauer-Kreisel, Petra T1 - Ischemia-like stress conditions stimulate trophic activities of adipose-derived stromal/stem cells JF - Cells N2 - Adipose-derived stromal/stem cells (ASCs) have been shown to exert regenerative functions, which are mainly attributed to the secretion of trophic factors. Upon transplantation, ASCs are facing an ischemic environment characterized by oxygen and nutrient deprivation. However, current knowledge on the secretion capacity of ASCs under such conditions is limited. Thus, the present study focused on the secretory function of ASCs under glucose and oxygen deprivation as major components of ischemia. After exposure to glucose/oxygen deprivation, ASCs maintained distinct viability, but the metabolic activity was greatly reduced by glucose limitation. ASCs were able to secrete a broad panel of factors under glucose/oxygen deprivation as revealed by a cytokine antibody array. Quantification of selected factors by ELISA demonstrated that glucose deprivation in combination with hypoxia led to markedly higher secretion levels of the angiogenic and anti-apoptotic factors IL-6, VEGF, and stanniocalcin-1 as compared to the hypoxic condition alone. A conditioned medium of glucose/oxygen-deprived ASCs promoted the viability and tube formation of endothelial cells, and the proliferation and migration of fibroblasts. These findings indicate that ASCs are stimulated by ischemia-like stress conditions to secrete trophic factors and would be able to exert their beneficial function in an ischemic environment. KW - adipose-derived stromal/stem cells (ASCs) KW - regenerative medicine KW - secretion KW - trophic factors KW - ischemia KW - glucose starvation KW - hypoxia Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211233 SN - 2073-4409 VL - 9 IS - 9 ER -