Vallée M, Côté J-F, Fradette J
Laboratoire d'organogénèse expérimentale (LOEX), hôpital du Saint-Sacrement-du-Chauq, 1050, chemin Sainte-Foy, G1S 4L8 Québec, Canada.
Pathol Biol (Paris). 2009 Jun;57(4):309-17. doi: 10.1016/j.patbio.2008.04.010. Epub 2008 Jun 4.
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.
脂肪组织现已被公认为是再生医学应用中产后间充质干细胞的重要来源。例如，脂肪组织工程是一种新兴方法，能够开发自体替代物，可作为目前脂肪移植方法的替代方案，脂肪移植方法目前在软组织缺损的长期修复中效果不一。在此，我们描述了由人脂肪来源的干/基质细胞产生的不含外源生物材料的独特组织工程化脂肪组织的制备。我们的策略基于脂肪来源的基质细胞在抗坏血酸刺激后分泌和组织的细胞外成分的双重自组装，以及它们在成脂诱导后伴随分化为脂肪细胞。与从切除的脂肪中分离的基质细胞相比，抽脂脂肪来源的细胞具有更高的成脂潜力和在体外重建三维脂肪替代物的增强能力。这些替代物在组织学上与天然脂肪组织相似。它们的特征是脂质填充的脂肪细胞嵌入富含纤连蛋白以及I型和V型胶原的细胞外基质中。在功能水平上，重建的脂肪组织表达脂肪细胞相关转录本并分泌脂肪组织特有的脂肪因子，如瘦素。最后，描述了成功在体外生产表面积增加（>30平方厘米）的人脂肪替代物，强化了未来可以生产定制的自体重建脂肪组织以修复广泛软组织缺损的观念。
