Identification of MAPC in the Walls of Human Fat Tissue Blood

描述(申请人提供)：人类白色脂肪组织(WAT)含有多潜能的中胚层前体细胞，这是几位研究人员分析整个组织的分化潜能后得出的结论，因此，它似乎是一种有吸引力的、方便的、廉价的和丰富的治疗性干细胞来源。在目前的初步研究中，我们着手直接鉴定这些脂肪组织驻留的干细胞。我们的总体策略直接受到包括我们自己在内的最近观察的启发，这些观察表明，血管内皮细胞和相关的壁细胞或周细胞可以成为造血系统、骨骼肌和胰腺早期祖细胞的来源。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血管基质中分离内皮细胞和周细胞，并将其引入检测系统，在培养和免疫缺陷小鼠中，以证明它们产生脂肪细胞、肌纤维和造血细胞的能力。了解从WAT等简单组织中分离出的单个细胞亚群的分化潜力，将是鉴定过去几年显示存在于成人器官中的难以捉摸的多潜能干细胞--间充质干细胞(MSC)、多潜能成体祖细胞(MAPC)或肌源性干细胞(MDSC)--的一步。脂肪组织含有难以捉摸的干细胞，如果特征更好，可以用来修复患病的器官，例如肌肉、骨骼甚至心脏。脂肪抽吸术通常在整容手术中进行，是一种安全而简单的手术，可以提供足够数量的此类治疗性干细胞。这些细胞应该被提纯，在某些情况下在培养中受到刺激，然后移植到待修复的组织中。我们正在鉴定多能干细胞在人类脂肪组织中的定位和分子特征。该项目将进一步记录这些细胞的特性，并确定它们未来的纯化方法，并将其发展成不同的人类功能组织。

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.