Abstract

Adipose tissue is now recognized as an important source of postnatal mesenchymal stem cells for regenerative medicine applications. For example, adipose-tissue engineering is an emerging approach that enables the development of autologous substitutes that could be used as an alternative to fat transplantation methods currently yielding variable outcomes for the long-term repair of soft-tissue defects. Here, we describe the production of unique tissue-engineered adipose tissues devoid of exogenous biomaterials produced from human adipose-derived stem/stromal cells. Our strategy is based on the dual self-assembly of extracellular components secreted and organized by the adipose-derived stromal cells after ascorbic acid stimulation, as well as their concomitant differentiation into adipocytes after adipogenic induction. When compared to stromal cells isolated from resected fat, lipoaspirated fat-derived cells featured an increased adipogenic potential and the enhanced ability to recreate three-dimensional adipose substitutes in vitro. These substitutes were histologically similar to native adipose tissue. They featured lipid-filled adipocytes embedded into an extracellular matrix rich in fibronectin as well as collagens I and V. On a functional level, the reconstructed adipose tissues expressed adipocyte-related transcripts and secreted adipokines typical of adipose tissue, such as leptin. Finally, the successful in vitro production of human adipose substitutes featuring an increased surface area (>30cm2) is described, reinforcing the notion that customized autologous reconstructed adipose tissues could be produced in the future to repair a wide range of soft-tissue defects.