Development of an adipose-derived stem cell isolation matrix

描述(由申请人提供)：在美国，每年大约进行500,000例骨移植手术。自体髂骨移植仍然是黄金标准，因为它提供了骨形成所必需的元素：祖细胞、骨传导基质和骨诱导分子。然而，取髂骨与大量的并发症有关，而且通常提供的移植物数量不足。为了克服这些局限性，多能间充质干细胞(MSCs)被添加到骨移植替代物中，并被探索用于组织工程应用，如脊柱融合和骨缺损修复。骨髓间充质干细胞(BMSCs)具有向中胚层来源的细胞和组织分化的能力，但在加工后的骨髓单个核成分中的比例很低。脂肪来源的干细胞(ASCs)已被建议作为BMSCs的替代细胞治疗，因为根据供者的不同，在加工过的脂肪抽提物的间质血管部分(SVF)中发现的多潜能ASCs的频率可以比骨髓抽吸物的单核部分(BMA)高数百倍。目前只有几种基本的护理设备来集中祖细胞，而祖细胞是促进骨愈合的基本要素。然而，这些设备是有限的，因为它们昂贵，因为它们要么浓缩非特定细胞群体，可能稀释所需细胞，要么利用抗体浓缩特定细胞群体，因此存在安全问题。在这个第二阶段的提案中，我们将开发一种用于骨移植的点式自体ASC浓缩系统，该系统不需要在植入前进行体外细胞扩增。

DESCRIPTION (provided by applicant): Approximately 500,000 bone-grafting procedures are performed each year in the United States. Autologous iliac crest bone graft continues to be the gold standard, because it provides essential elements for bone formation: progenitor cells, an osteoconductive matrix, and osteoinductive molecules. However, iliac crest harvest is associated with a significant number of complications and often provides an inadequate volume of graft. To overcome these limitations, multipotent Mesenchymal Stem Cells (MSCs) have been added to bone graft substitutes and explored for use in tissue engineering applications, such as spinal fusions and bone defect repairs. Bone marrow derived mesenchymal stem cells (BMSCs) are well characterized in their ability to differentiate into cells and tissues of mesodermal origin; however, their frequency in the mononuclear fraction of processed bone marrow is very low. Adipose derived stem cells (ASCs) have been proposed as an alternative to BMSCs for cell therapy because the frequency of multipotent ASCs found in the stromal vascular fraction (SVF) of processed lipoaspirate can be several hundred-fold greater than the mononuclear fraction of bone marrow aspirate (BMA), depending on the donor. Currently there are only a few basic point-of-care devices to concentrate progenitor cells, which are essential elements to foster bone healing. However, these devices are limiting because they are expensive and because they either enrich a non-specific cell population potentially diluting out desired cells or they enrich a specific cell population using antibodies and consequently have safety concerns. In this phase 2 proposal, we will develop a point-of-care autologous ASC enrichment system for bone grafting that eliminates the need for ex vivo cell expansion prior to implantation.