title: A multifunctional 3D co-culture system for studies of mammary tissue morphogenesis and stem cell biology.
abstract: Studies on the stem cell niche and the efficacy of cancer therapeutics require complex multicellular structures and interactions between different cell types and extracellular matrix (ECM) in three dimensional (3D) space. We have engineered a 3D in vitro model of mammary gland that encompasses a defined, porous collagen/hyaluronic acid (HA) scaffold forming a physiologically relevant foundation for epithelial and adipocyte co-culture. Polarized ductal and acinar structures form within this scaffold recapitulating normal tissue morphology in the absence of reconstituted basement membrane (rBM) hydrogel. Furthermore, organoid developmental outcome can be controlled by the ratio of collagen to HA, with a higher HA concentration favouring acinar morphological development. Importantly, this culture system recapitulates the stem cell niche as primary mammary stem cells form complex organoids, emphasising the utility of this approach for developmental and tumorigenic studies using genetically altered animals or human biopsy material, and for screening cancer therapeutics for personalised medicine.
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom. jjc55@cam.ac.uk
authors: Jonathan J
authors: JJ
authors: Campbell
authors: Natalia
authors: N
authors: Davidenko
authors: Maria M
authors: MM
authors: Caffarel
authors: Ruth E
authors: RE
authors: Cameron
authors: Christine J
authors: CJ
authors: Watson
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D018920:Coculture Techniques / Q000379:methods*; D003094:Collagen; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D013234:Stem Cells / Q000166:cytology*; D046509:Tissue Culture Techniques / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D006820:Hyaluronic Acid; D003094:Collagen