Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH 44106, United States.
Biomaterials. 2011 Dec;32(36):9667-76. doi: 10.1016/j.biomaterials.2011.08.090. Epub 2011 Sep 28.
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.
对软组织替代品的需求增加促使人们开发出了一种体外脂肪组织。理想情况下，这种组织应该包含一个血管网络，以便在移植后为整个构建物输送血液。本研究描述了一种完全采用自组装方法制备预血管化脂肪组织的方法。成年人体脂肪基质细胞（ASCs）为该构建物提供了基础。这些细胞在高浓度的抗坏血酸存在下培养，并在诱导脂肪生成之前进行培养。真皮成纤维细胞、脂肪基质细胞和骨髓间充质干细胞（MSCs）的混合物作为血管支持细胞被引入，以维持由人脐静脉内皮细胞（HUVEC）形成的广泛血管网络。MSCs 被引入作为血管周围细胞。由此产生的构建物包含一个血管-脂肪组织连续体，由基底膜分子连接在一起。该构建物包含多种通常存在于脂肪组织中的细胞类型：脂肪细胞、前脂肪细胞、干细胞、成纤维细胞、血管细胞和血管周围支持细胞。因此，这些构建物既可以用于体外研究，以检测血管和脂肪组织其他成分之间的细胞相互作用，也可以移植到无胸腺宿主中，以研究血管和脂肪细胞的稳定性。
