title: Sequential culture on biomimetic nanoclay scaffolds forms three-dimensional tumoroids.
abstract: In recent times, the limitation of two-dimensional cultures and complexity of in vivo models has paved the way for the development of three-dimensional models for studying cancer. Here we report the development of a new tumor model using PCL/HAPClay scaffolds seeded with a sequential culture of human mesenchymal stem cells (hMSCs) followed by human prostate cancer cells (HPCCs). This nanocomposite system is used as a test-bed for studying cancer metastasis and efficacy of anti-cancer drugs using a polymersome delivery method. A novel sequential cell culture system in three-dimensional in vitro bone model provides a unique bone mimetic environment. The hMSCs seeded scaffolds are seeded with prostate cancer cells after the hMSCs have differentiated into osteoblasts. Sequential culture on the scaffolds has shown formation of tumoroids or microtissue consisting of organized, densely packed round cells with hypoxic core regions similar to in vivo tumors. Such tumoroids are not observed on HPCC seeded scaffolds or when HPCCs sequentially cultured with human osteoblast cells. Clearly, the newly differentiated hMSCs play a vital role in the ability of cancer cells to grow into tumoroids and cause disease. The PCL/HAPclay scaffold system seeded with the sequential culture of hMSCs, and HPCCs presents a good model system for study of the interactions between prostate cancer cells and bone microenvironment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1591-1602, 2016.
authors.affiliation: Department of Civil and Environmental Engineering, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Kalpana S
authors.initials: KS
authors.lastname: Katti
authors.affiliation: Department of Civil and Environmental Engineering, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Md Shahjahan
authors.initials: MS
authors.lastname: Molla
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Fataneh
authors.initials: F
authors.lastname: Karandish
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Manas K
authors.initials: MK
authors.lastname: Haldar
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Sanku
authors.initials: S
authors.lastname: Mallik
authors.affiliation: Department of Civil and Environmental Engineering, North Dakota State University, Fargo, North Dakota, 58105.
authors.forename: Dinesh R
authors.initials: DR
authors.lastname: Katti
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000538:Aluminum Silicates / Q000737:chemistry*; D040761:Biomimetic Materials / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077215:Clay; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000494:pharmacology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D010012:Osteogenesis / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000473:pathology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D000538:Aluminum Silicates; D005492:Folic Acid; D000469:Alkaline Phosphatase; D000077215:Clay
keywords: cancer; metastasis; nanoclays; scaffolds; sequential culture; tumoroids