title: The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.
abstract: Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry.
authors.affiliation: Biological Systems Engineering Laboratory, Department of Chemical Engineering and Chemical Technology, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
authors.forename: Teresa Mortera
authors.initials: TM
authors.lastname: Blanco
authors.forename: Athanasios
authors.initials: A
authors.lastname: Mantalaris
authors.forename: Alexander
authors.initials: A
authors.lastname: Bismarck
authors.forename: Nicki
authors.initials: N
authors.lastname: Panoskaltsis
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry / Q000378:metabolism; D001854:Bone Marrow Cells / Q000737:chemistry / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D008422:Materials Testing; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019904:Polymethyl Methacrylate / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D011140:Polyurethanes / Q000737:chemistry; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D011091:Polyesters; D011137:Polystyrenes; D011140:Polyurethanes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D019904:Polymethyl Methacrylate