Title : A 3D-bioprinted in vitro adipose tissue model for the study of macrophage polarisation and function within metabolic disease.
Abstract:
Macrophages dynamically polarise into specialised phenotypes to perform an array of functions as part of both the innate immune response and tissue homeostasis. The ability of macrophages to polarise stems from the sensitivity of these cells to the local tissue environment. The composition of the extracellular matrix has been observed to induce macrophage polarisation and modulate macrophage function through providing both mechanical cues and controlling the concentration gradients of key factors. Here, the polarisation and function of human macrophages is comprehensively characterised within a 3D bio-printed collagen-based hydrogel in comparison to standard 2D culture. We observe that macrophages retain morphology, viability, and expression of key cell surface markers throughout 3D culture. Within adipose tissue the crosstalk between macrophages and adipocytes underlies the pathogenesis of metabolic disease. Utilising the workflow established here we investigate the phenotype and polarisation of macrophages in response to adipocytes changes induced by metabolic disorders. Further, through a bespoke high-throughput image analysis pipeline the interaction dynamics between macrophages and these adipocytes within the 3D space are analysed. This comprehensive characterisation of macrophages within 3Dbioprinted models is essential for understanding the phenotype of these highly responsive cells, and for the recapitulation of in vivo microenvironments for the study and potential modulation of macrophage behaviour within specific biological states.
Audience Take Away:
- This comprehensive study of macrophages within 3D hydrogel culture highlights the benefits of utilising a 3D culture method in comparison to standard 2D macrophage cultures.
- The use of flow cytometry, high-throughput confocal imaging, and secretion profile analysis used here illustrates a powerful tool-box of techniques that can be utilised for the characterisation of macrophage polarisation within 3D environments.
- This 3D subcutaneous tissue model highlights the interactions between macrophages and adipocytes in the context of metabolic disease.
