Human induced pluripotent stem cell-derived neurons and coculture conditions regulate the adipogenic differentiation and functionality of human adipose stromal/stem cells.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The obesity epidemic and associated diseases have increased the need to study human adipose tissue biology and, furthermore, the development of in vitro models of adipose tissues. Human adipose tissue innervation is a relatively understudied research area, and most studies have been performed in animal models. A common animal model is the mouse, which differs from humans in many areas, such as fat distribution, metabolism and genetics. Here, our aim was to develop a three-dimensional (3D) neuro-adipose in vitro model with human-derived cells to deepen the understanding of adipose tissue innervation. We hypothesized that our novel, optimized coculture conditions for neurons and adipose stromal/stem cells (ASCs) would enhance the adipogenesis of ASCs and the functionality of differentiating ASC-derived adipocytes. In this study, a novel 3D in vitro culture of adipocytes innervated on a microfluidic chip utilizing human ASCs and human induced pluripotent stem cell (hiPSC)-derived neurons was established. The cells were cultured in a fibrin-collagen 1 hydrogel in a microfluidic environment for a long period (≥ 21 days) in neuro-adipose combination medium (NM-AM). The adipogenic differentiation of ASCs and adipose cell functions, such as fatty acid (FA) uptake, lipolysis and adipokine secretion, were analyzed. In addition, cell activity was examined with calcium activity measurement

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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