Adipocytes are specialized cells with pleiotropic roles in physiology and pathology. Several types of fat cells with distinct metabolic properties co-exist in various anatomically defined fat depots in mammals. White, beige and brown adipocytes differ in their handling of lipids and thermogenic capacity promoting differences in size and morphology. Moreover, adipocytes release lipids and proteins with paracrine and endocrine functions. The intrinsic properties of adipocytes pose specific challenges in culture. Mature adipocytes float in suspension culture due to high triacylglycerol content and are fragile. Moreover, a fully differentiated state, notably acquirement of the unilocular lipid droplet of white adipocyte, has so far not been reached in two-dimensional culture. Cultures of mouse and human differentiated preadipocyte cell lines and primary cells have been established to mimic white, beige and brown adipocytes. Here, we survey various models of differentiated preadipocyte cells and primary mature adipocyte survival describing main characteristics, culture conditions, advantages and limitations. An important development is the advent of three-dimensional culture, notably of adipose spheroids that recapitulate in vivo adipocyte function and morphology in fat depots. Challenges for the future include isolation and culture of adipose-derived stem cells from different anatomical location in animal models and humans differing in sex, age, fat mass and pathophysiological conditions. Further understanding of fat cell physiology and dysfunction will be achieved through genetic manipulation, notably CRISPR-mediated gene editing. Capturing adipocyte heterogeneity at single cell level within a single fat depot will be key to understand diversities in cardiometabolic parameters among lean and obese individuals.
Background. Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids.Methods. We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth. We exhibit the crucial importance of the effective surface tension, and of the inner pressure of the spheroid to describe precisely the fusion. The experimental data were obtained on spheroids of colon carcinoma human cells (HCT116 cell line). After 3 or 6 days of culture, two identical spheroids were transferred in one well and their fusion was monitored by live videomicroscopy acquisition each 2hours during 72h. From these images the neck radius and the diameter of the assembly of the fusing spheroids are extracted.Results. The numerical model is fitted with the experiments. It is worth noting that the time evolution of both neck radius and spheroid diameter are quantitatively obtained. The interesting feature lies in the fact that such measurements characterise the macroscopic rheological properties of the tumor spheroids. * guillaume.dechriste@gmail.com † jerome.fehrenbach@math.univ-toulouse.fr ‡ elena.griseti@ipbs.fr § Valerie.lobjois@itav.fr ¶ Corresponding author, clair.poignard@inria.fr 1 Conclusions. The experimental determination of the kinetics of neck radius and overall diameter during spheroids fusion characterises the rheological properties of the spheroids. The consistency of the model is shown by fitting the model with two different experiments, enhancing the importance of both surface tension and cell proliferation.General Significance. The paper sheds new light on the macroscopic rheological properties of tumor spheroids. It emphasizes the role of the surface tension and the inner pressure in the fusion of growing spheroid. Under geometrical assumptions, the model reduces to a 2-parameter differential equation fit with experimental measurements. The 3-D partial differential system makes it possible to study the fusion of spheroids in non-symmetrical or more general frameworks.
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