Vascularizing Adipose Organoids (vAOs) in vitro

Organoids are invaluable tools for disease modeling and high throughput screening. The majority of organoids contain one or two cell types, that aggregate to form a homogenous spheroid structure. Rarely in the body, however, are tissues so homogenous. In addition to specialized cells, tissues contain a vasculature and a spectrum of other cell types. Not only does the vasculature provide perfusion, but the additional vessel-associated cell types engage in complex signaling with other tissue components and aid in overall tissue function. Thus, the more of these varied cell types in a tissue model or organoid, the better the model biology matches the native tissue. At Advanced Solutions, we utilized whole, intact, microvessel fragments, isolated from human lipoaspirates (Angiomics® haMVs), to vascularize MSC-derived adipose organoids to enhance model adipose tissue function.

haMVs were combined with either MSCs or MSC-derived preadipocytes (for adipose organoids) and cultured alone or embedded in 3D matrix. When embedded, new vessels grew out of the organoids and into the surrounding matrix within 2 days (Fig 1). Further, in adipose organoids, neovascular networks appear more

mature, with branching and connecting vessels (Fig 1B). Adipose organoids accumulated large lipid droplets (Fig 2A) and expressed adipocyte markers adiponectin and PPARγ (Fig 2B), demonstrating differentiation into mature adipocytes. Highlighting the influence of the haMVs, insulin receptor expression by the adipocytes was upregulated in organoids with microvessels, compared to control organoids without microvessels (Fig 3A-C).

ASLS has developed a vascularized, human adipose organoid (vAO) to model adipose tissue biology in vitro using a simple and robust approach involving isolated, intact microvessel fragments (haMVs). VAOs exhibit typical adipose tissue functionality, including responses to inflammatory mediators and active insulin receptor expression that would facilitate insulin resistance studies. Additionally, the vascular component of the vAO retains angiogenic potential suggesting, that if implanted, they will engraft with the surrounding tissue. While the ASLS vascularization approach was demonstrated with MSC and adipose organoids, the fabrication procedure is broadly applicable to other tissue model systems as well.

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