title: Quantifying the correlation between spatially defined oxygen gradients and cell fate in an engineered three-dimensional culture model.
abstract: A challenge in three-dimensional tissue culture remains the lack of quantitative information linking nutrient delivery and cellular distribution. Both in vivo and in vitro, oxygen is delivered by diffusion from its source (blood vessel or the construct margins). The oxygen level at a defined distance from its source depends critically on the balance of diffusion and cellular metabolism. Cells may respond to this oxygen environment through proliferation, death and chemotaxis, resulting in spatially resolved gradients in cellular density. This study extracts novel spatially resolved and simultaneous data on tissue oxygenation, cellular proliferation, viability and chemotaxis in three-dimensional spiralled, cellular collagen constructs. Oxygen concentration gradients drove preferential cellular proliferation rates and viability in the higher oxygen zones and induced chemotaxis along the spiral of the collagen construct; an oxygen gradient of 1.03 mmHg mm(-1) in the spiral direction induced a mean migratory speed of 1015 μm day(-1). Although this movement was modest, it was effective in balancing the system to a stable cell density distribution, and provided insights into the natural cell mechanism for adapting cell number and activity to a prevailing oxygen regime.
authors: University College London, Tissue Repair and Engineering Centre, Institute for Orthopaedics and Musculoskeletal Sciences, Stanmore Campus, London HA7 4LP, UK.
authors: Amir G
authors: AG
authors: Ardakani
authors: University College London, Tissue Repair and Engineering Centre, Institute for Orthopaedics and Musculoskeletal Sciences, Stanmore Campus, London HA7 4LP, UK.
authors: Umber
authors: U
authors: Cheema
authors: University College London, Tissue Repair and Engineering Centre, Institute for Orthopaedics and Musculoskeletal Sciences, Stanmore Campus, London HA7 4LP, UK.
authors: Robert A
authors: RA
authors: Brown
authors: University College London, Tissue Repair and Engineering Centre, Institute for Orthopaedics and Musculoskeletal Sciences, Stanmore Campus, London HA7 4LP, UK University College London, Biomechanical Engineering Group, Department of Mechanical Engineering, London WC1E 7JE, UK rebecca.shipley@ucl.ac.uk.
authors: Rebecca J
authors: RJ
authors: Shipley
mesh_terms: D018929:Cell Culture Techniques; D016923:Cell Death; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D002633:Chemotaxis; D003094:Collagen / Q000737:chemistry; D004058:Diffusion; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional; D010100:Oxygen / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D003094:Collagen; D010100:Oxygen
keywords: biocompatibility; cell culture; collagen; tissue engineering