A causal relation between bioluminescence and oxygen to quantify the cell niche.
Bioluminescence imaging assays have become a widely integrated technique to quantify effectiveness of cell-based therapies by monitoring fate and survival of transplanted cells. To date these assays are still largely qualitative and often erroneous due to the complexity and dynamics of local micro-environments (niches) in which the cells reside. Here, we report, using a combined experimental and computational approach, on oxygen that besides being a critical niche component responsible for cellular energy metabolism and cell-fate commitment, also serves a primary role in regulating bioluminescent light kinetics. We demonstrate the potential of an oxygen dependent Michaelis-Menten relation in quantifying intrinsic bioluminescence intensities by resolving cell-associated oxygen gradients from bioluminescent light that is emitted from three-dimensional (3D) cell-seeded hydrogels. Furthermore, the experimental and computational data indicate a strong causal relation of oxygen concentration with emitted bioluminescence intensities. Altogether our approach demonstrates the importance of oxygen to evolve towards quantitative bioluminescence and holds great potential for future microscale measurement of oxygen tension in an easily accessible manner.
Department of Metallurgy and Materials Engineering, KU Leuven, Leuven, Belgium; Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium.
Dennis
D
Lambrechts
Center for Surface Chemistry and Catalysis, KU Leuven, Leuven, Belgium.
Maarten
M
Roeffaers
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas, United States of America.
Karel
K
Goossens
Molecular Imaging and Photonics, KU Leuven, Leuven, Belgium.
Johan
J
Hofkens
Greetje
G
Vande Velde
TiGenix NV, Leuven, Belgium.
Tom
T
Van de Putte
Department of Metallurgy and Materials Engineering, KU Leuven, Leuven, Belgium; Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium.
Jan
J
Schrooten
Prometheus, Division of Skeletal Tissue Engineering Leuven, KU Leuven, Leuven, Belgium; Biomechanics Section, KU Leuven, Leuven, Belgium.
Hans
H
Van Oosterwyck
D002460:Cell Line; D006801:Humans; D020100:Hydrogels; D008163:Luminescent Measurements; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism*
D020100:Hydrogels; D010100:Oxygen