Development of an adipose-derived stem cell isolation matrix

脂肪干细胞分离基质的开发

• 批准号: 8702193
• 负责人: Martyn Darby
• 金额: $ 78.92万
• 依托单位: AFFINERGY, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8702193
• 关键词: Adipose tissue; Adult; Affect; Affinity; Antibodies; Area; Aspirate substance; Autologous; Binding; Biocompatible Materials; Biodegradation; Biological; Biological Assay; Biomechanics; Blood Vessels; Bone Marrow; Bone Transplantation; Cell Separation; Cell Therapy; Cells; Clinical; Collagen; Complex; Defect; Development; Devices; Drug Formulations; Elements; Engineering; Evaluation; Fee-for-Service Plans; Fostering; Fracture; Frequencies; Gene Expression; Goals; Gold; Growth Factor; Harvest; Histology; Implant; Liquid substance; Manuals; Mesenchymal Stem Cells; Modeling; Mononuclear; Multipotent Stem Cells; Operating Rooms; Operative Surgical Procedures; Organ Transplantation; Orthopedic Surgery procedures; Orthopedics; Oryctolagus cuniculus; Osteogenesis; Palpation; Patients; Peptide Synthesis; Peptides; Phage Display; Pharmaceutical Preparations; Phase; Population; Process; Protocols documentation; Publishing; Reagent; Rest; Safety; Series; Speed; Spinal Fusion; Stem cells; Sterilization; Surgeon; System; Technology; Testing; Tissue Engineering; Tissues; United States; Vertebral column; Work; adult stem cell; biomaterial compatibility; bone; bone healing; clinical practice; cost; design; flexibility; immunogenicity; implantation; improved; innovation; osteogenic; point of care; protein aminoacid sequence; prototype; repaired; research study; scaffold; scale up; screening; self-renewal; tricalcium phosphate

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.

描述（由申请人提供）：美国每年进行大约 500,000 例骨移植手术。自体髂嵴骨移植仍然是黄金标准，因为它提供了骨形成的必需元素：祖细胞、骨​​传导基质和骨诱导分子。然而，髂嵴切除与大量并发症相关，并且常常提供的移植物体积不足。为了克服这些限制，多能间充质干细胞（MSC）已被添加到骨移植替代品中，并探索用于组织工程应用，例如脊柱融合和骨缺损修复。骨髓间充质干细胞 (BMSC) 具有分化为中胚层来源的细胞和组织的能力；然而，它们在处理过的骨髓的单核部分中的频率非常低。脂肪干细胞 (ASC) 已被提议作为 BMSC 的替代品用于细胞治疗，因为在加工的脂肪抽吸物的基质血管部分 (SVF) 中发现的多能 ASC 的频率可能比骨髓抽吸物 (BMA) 的单核部分高数百倍，具体取决于供体。目前只有几种基本的护理点设备可以集中祖细胞，而祖细胞是促进骨愈合的基本要素。然而，这些设备具有局限性，因为它们价格昂贵，并且因为它们要么富集非特异性细胞群，可能稀释所需细胞，要么它们使用抗体富集特定细胞群，因此存在安全问题。在这个第二阶段提案中，我们将开发一种用于骨移植的即时自体 ASC 富集系统，消除植入前离体细胞扩增的需要。