Isolated human adipose microvessels retain native microvessel structure and recapitulate sprouting angiogenesis

Abstract

With interest growing in modeling more complex aspects of human disease in the laboratory, the need for effectively vascularizing human tissue models is becoming paramount. However, fully recreating human tissue microvasculatures is challenging given the multicellular complexity of the microvessel and microvessel-tissue interplay. Importantly, effective models should capture the dynamic activity of the perivascular cells of the perivascular niche, which are critical to tissue hemostasis and function. Isolated microvessel fragments from rodent adipose have been extensively studied and used in a variety of vascularization models. We have progressed this proven technology by deriving isolated fragments of intact human microvessels harvested from adipose (haMVs) to model human vascularization and advance human vascularized tissue models. Here we show the haMVs retain native microvessel structures, including perivascular cellularity, and recapitulate bona fide sprouting angiogenesis in vitro through distinct sprouting and neovessel elongation phases. As primary isolates, the angiogenic potential varies between donor lots and correlates with the presence of haMV perivascular cells. In an in vitro model of tumor angiogenesis, the addition of anti-tumor agents impacted tumor cell expansion in the presence of the haMVs but not endothelial cells alone demonstrating the importance of the perivascular cells in tissue modeling. The human adipose microvessels offer, in a single reagent, a more complex, dynamic human tissue model vascularization solution.

Graphical Abstract