Point of Care Adult Stem Cell Isolation

护理点成人干细胞分离

• 批准号: 8057888
• 负责人: Hanne Gron
• 金额: $ 3.53万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8057888
• 关键词: Address; Adipose tissue; Affinity; Animal Model; Antibodies; Aspirate substance; Autologous; Benchmarking; Binding; Biocompatible Materials; Biological; Biological Assay; Bone Marrow; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Calvaria; Caring; Cell Separation; Cell Therapy; Cells; Clinical; Complex; Contracts; Defect; Degenerative polyarthritis; Development; Devices; Disease; Elements; Engineering; Ensure; Filtration; Fostering; Fracture; Gold; Growth Factor; Harvest; Human; Implant; Libraries; Ligaments; Liquid substance; Manufacturer Name; Mediating; Mesenchymal Stem Cells; Methods; Modeling; Mutagenesis; Operating Rooms; Organ Transplantation; Orthopedic Surgery procedures; Orthopedics; Osteogenesis; Patients; Peptide Hydrolases; Peptide Synthesis; Peptides; Phage Display; Pharmaceutical Preparations; Phase; Physicians; Polystyrenes; Population; Preparation; Property; Proteins; Rattus; Research; Rest; Safety; Sampling; Screening procedure; Seed Implantation; Series; Site; Small Business Innovation Research Grant; Solid; Spinal Fusion; Stem cells; Sterilization; System; Technology; Tendon structure; Testing; Therapeutic; Tissue Engineering; Tissues; Transplanted tissue; Work; Wound Healing; adult stem cell; biomaterial compatibility; bone; bone healing; cell type; commercialization; cost effective; design; design and construction; experience; flexibility; improved; in vivo; innovation; multipotent cell; osteoinductive factor; point of care; product development; programs; protein aminoacid sequence; prototype; research study; scale up

DESCRIPTION (provided by applicant): Approximately 500,000 bone-grafting procedures are performed each year in the United States.5 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.6 To address these limitations, much work has been done to improve alternative grafts with better osteoconductive matrices and exogenous delivery of osteoinductive agents such as the bone morphogenetic proteins (BMPs).7 Currently there are only a few basic point-of-care devices to isolate 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. Therefore, a safe, inexpensive device that could enrich adult stem cells from a bone marrow aspirate (BMA) or other tissue stroma at point-of-care would be of significant clinical benefit. In this phase II proposal, we will continue to develop a cell isolation device to enrich the multipotent subpopulation of cells in human bone marrow known as mesenchymal stem cells (MSCs). (*2)Furthermore, we will demonstrate versatility of the isolation device by showing that we can capture adult stem cells from adipose tissue. The advantage of adipose tissue is the availability of greater numbers of bone healing cells. We have identified and synthesized an MSC-binding peptide that can isolate adult stem cells from bone marrow and adipose tissue, and these isolated cells are multipotent. The MSC-binding peptide will be covalently attached to a solid support matrix and will form the functional core of the cell isolation device. The cells isolated will be captured and released using the prototype device, and different concentrations of cells will be tested in bone healing of a rat calvarial defect. An isolated pool of MSCs has the potential to serve key clinical functions in a range of indications including osteoarthritis, Chron's disease and soft tissue repair such as tendon, ligament or wounds. This product will provide a safe and cost-effective point-of-care isolation system for the preparation of autologous cells. PUBLIC HEALTH RELEVANCE: Bone grafting is widely used in orthopedic surgery to treat fractures and large bone defects and to achieve spinal fusions. However, harvesting a bone graft from patients is associated with a significant number of complications and often provides an inadequate amount of tissue. While alternatives to bone grafts have shown promise, there is still room for considerable improvement. Therefore, a device, like the one proposed in this SBIR application, that could isolate adult stem cells efficiently and quickly in the operating room would be of significant clinical benefit in a number of clinical indications.

描述（由申请人提供）：在美国，每年大约进行500,000个骨夹程序。5自体裂骨移植物仍然是黄金标准，因为它为骨形成提供了必不可少的元素：祖细胞，骨化细胞，骨失位基矩阵和骨诱导分子。然而，伊利亚克·克雷斯特（Iliac Crest）的收获与大量的并发症有关，并且通常会提供不足的移植物。6为了解决这些局限性，已经做出了许多工作，以改善具有更好骨的矩阵的替代移植物和骨气诱导剂的外源性剂量的骨骼感应剂，例如骨形蛋白（bmps）的骨骼形成蛋白（bmps）。促进骨骼愈合的基本要素。但是，这些设备之所以限制，是因为它们很昂贵，并且因为它们要么富含潜在稀释所需细胞的非特异性细胞群，要么使用抗体富含特定的细胞群，因此存在安全问题。因此，可以从骨髓抽吸物（BMA）或护理点上的其他组织基质中富含成年干细胞的安全，廉价的装置将具有显着的临床益处。 在此II期提案中，我们将继续开发一个细胞分离装置，以丰富称为间充质干细胞（MSC）的人骨髓中细胞的多能亚群。 （*2）此外，我们将通过证明我们可以从脂肪组织中捕获成年干细胞来证明隔离装置的多功能性。脂肪组织的优点是骨骼愈合细胞的可用性。我们已经确定并合成了一种MSC结合肽，该肽可以将成年干细胞与骨髓和脂肪组织分离，这些分离的细胞是多能。 MSC结合肽将共价连接到固体支撑矩阵上，并形成细胞隔离装置的功能核心。分离的细胞将被捕获并使用原型装置释放，并且不同浓度​​的细胞将在大鼠颅骨缺陷的骨骼愈合中进行测试。孤立的MSC库具有在包括骨关节炎，Chron病和软组织修复（如肌腱，韧带或伤口）的一系列适应症的范围内发挥关键临床功能的潜力。该产品将提供一个安全且具有成本效益的护理隔离系统，以制备自体细胞。 公共卫生相关性：骨移植被广泛用于骨科手术中，以治疗裂缝和巨大的骨缺损并实现脊柱融合。但是，从患者那里收集骨移植物与大量并发症有关，并且通常提供不足的组织。虽然骨移植物的替代方案已经显示出希望，但仍有大量改善的空间。因此，像该SBIR应用中提出的那样，可以在许多临床适应症中有效地隔离成年干细胞的设备将具有显着的临床益处。