Identification of MAPC in the Walls of Human Fat Tissue Blood

描述（由申请人提供）：人白色脂肪组织（WAT）含有多能中胚层祖细胞，如几位研究者分析整个组织的分化潜能所推断的，因此，似乎是治疗性干细胞的有吸引力的、方便的、廉价的和丰富的来源。在目前的试点研究中，我们开始直接识别这些脂肪组织驻留干细胞。我们的总体策略直接受到最近观察的启发，包括我们自己的观察，表明血管内皮细胞和相关的壁细胞或周细胞可以是造血系统、骨骼肌和胰腺中早期祖细胞的来源。我们在本项目中测试的假设是，这也适用于脂肪组织。为此，将通过流式细胞术从人WAT血管基质中分选内皮细胞和周细胞至均一性，并在培养物和免疫缺陷小鼠中引入测定系统中，以记录其产生脂肪细胞、肌纤维和造血细胞的能力。了解从简单组织（如WAT）中分选的单个细胞亚群的分化潜力将是识别难以捉摸的多能干细胞的一步-间充质干细胞（MSC），多能成体祖细胞（MAPC）或肌源性干细胞（MDSC）-在过去几年中显示存在于成人器官中。脂肪组织含有难以捉摸的干细胞，如果能更好地表征，这些干细胞可以用于修复患病的器官，例如肌肉，骨骼甚至心脏。脂肪抽吸术通常在美容手术中进行，是一种安全简便的手术，可以提供足够数量的治疗性干细胞。这些细胞应该被纯化，在某些情况下在培养物中刺激，然后移植到待修复的组织中。我们正在确定人类脂肪组织中多能干细胞的定位和分子特征。该项目将进一步记录这些细胞的特性，并确定其预期纯化和发展为多种人类功能组织的方法。

DESCRIPTION (provided by applicant): Human white adipose tissue (WAT) contains multipotent mesodermal progenitors, as deduced by several investigators who assayed the differentiation potential of the whole tissue, and, therefore, appears as an attractive, convenient, cheap and abundant source of therapeutic stem cells. In the present pilot study, we embark on the direct identification of these fat tissue-resident stem cells. Our general strategy is directly inspired by recent observations that include our own, showing that vascular endothelial cells and related mural cells, or pericytes, can be the source of early progenitors in the hematopoietic system, skeletal muscle and pancreas. The hypothesis we test in the present project is that this also applies to adipose tissue. To this end, endothelial cells and pericytes will be sorted to homogeneity, by flow cytometry, from the human WAT vascular stroma and introduced into assay systems, in culture and in immunodeficient mice, in order to document their ability to give rise to adipocytes, myofibers and hematopoietic cells. Understanding the differentiation potential of individual cell subsets sorted from a simple tissue such as WAT will be a step toward the identification of the elusive multipotent stem cells - mesenchymal stem cells (MSC), multipotent adult progenitor cells (MAPC) or muscle-derived stem cells (MDSC) - shown in the past few years to reside in adult organs. Fat tissue contains elusive stem cells that, if better characterized, could be used to repair diseased organs, for instance the muscle, bones and even the heart. Fat aspiration, which is commonly performed in cosmetic surgery, is a safe and easy procedure that could provide sufficient amounts of such therapeutic stem cells. These should be purified, in some instances stimulated in culture, then transplanted into the tissue to be repaired. We are in the process of identifying the localization and molecular characteristics of multipotent stem cells within human fat tissue. This project will further document the properties of these cells and lead to define methods for their prospective purification and development into diverse human functional tissues.