The creation of an in vitro adipose tissue that contains a vascular-adipocyte complex

Abstract

An increased demand for soft-tissue substitutes has impelled the development of an in vitro adipose tissue. Ideally, such a tissue should contain a vascular network that can deliver blood throughout the construct following its engraftment. This study describes the in vitro fabrication of a pre-vascularized adipose tissue entirely using a self-assembly approach. Adult human adipose stromal cells (ASCs) provided the foundation for this construct. These cells were cultured at high density in the presence of elevated levels of ascorbate prior to adipocytic induction. Vascular support cells consisting of dermal fibroblasts, mixtures of adipose stromal cells and bone marrow mesenchymal stem cells (MSCs) were introduced to sustain an extensive vascular network formed by human umbilical vein endothelial cells (HUVECs). MSCs were introduced to serve as perivascular cells. The resulting construct contained a vascular-adipose tissue continuum that was held together by basement membrane molecules. This construct contains multiple cell types that are typically found in adipose tissue: adipocytes, pre-adipocytes, stem cells, fibroblasts, vascular cells, and perivascular support cells. As such, these constructs can be employed both for in vitro studies to assay cellular interactions between vasculature and other components of adipose tissue. Further, they can also be engrafted into athymic hosts to study vascular and adipocyte stability.