Adipose-tissue engineering: Taking advantage of the properties of human adipose-derived stem/stromal cells

• Published in: Pathologie biologie (Paris) 2009-06, Vol.57 (4), p.309-317
• Main Authors: Vallée, M., Côté, J.-F., Fradette, J.
• Format: Article
• Language: English
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; Adipocytes; Adipocytes - cytology; Adipocytes - drug effects; Adipocytes - metabolism; Adipose tissue; Adult; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Ascorbic Acid - pharmacology; Autoassemblage; Autologous; Cell Culture Techniques - methods; Cell Differentiation; Cells, Cultured - cytology; Cellules souches; Extracellular matrix; Extracellular Matrix - metabolism; Female; Glyceraldehyde-3-Phosphate Dehydrogenases - biosynthesis; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Génie tissulaire; Humans; Leptin - biosynthesis; Leptin - genetics; Leptin - secretion; Lipectomy; Lipoprotein Lipase - biosynthesis; Lipoprotein Lipase - genetics; Matrice extracellulaire; PPAR gamma - biosynthesis; PPAR gamma - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Self-assembly; Serum; Stem cells; Stromal Cells - cytology; Stromal Cells - metabolism; Subcutaneous Fat - cytology; Thiazolidinediones - pharmacology; Tissu adipeux; Tissue engineering; Tissue Engineering - methods; Tissus reconstruits autologues
• ISSN: 0369-8114; 1768-3114
• DOI: 10.1016/j.patbio.2008.04.010

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 (> 30 cm 2) 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. Les cellules stromales du tissu adipeux représentent une source abondante et accessible de cellules souches mésenchymateuses postnatales revêtant un grand intérêt en médecine régénératrice. Par exemple, la reconstruction in vitro de tissu adipeux est une approche émergente visant à développer des tissus de remplacement comme alternative aux méthodes actuelles de transplantation de tissu adipeux. Nous avons produit, par génie tissulaire, des tissus adipeux humains exempts de biomatériau exogène. Notre stratégie est basée sur une méthode d’autoassemblage adaptée qui permet aux cellules souches/stromales extraites du tissu adipeux de sécréter et d’organiser des éléments de la matrice extracellulaire suite à une stimulation avec l’acide ascorbique et, en parallèle, de se différencier en ad