USE OF ADIPOSE-DERIVED PREADIPOCYTES IN BONE DISOREDERS

不愈合性骨折和牙周骨丢失构成显著的临床 只有少数几种经批准的医疗选择。骨修复是由 存在成骨细胞或成骨前体细胞。皮下脂肪组织 是一个丰富的，可获得的，可再生的人类基质细胞来源， 移植在SBIR的第一阶段，我们测试了人类脂肪 组织来源的基质细胞能够具有成骨细胞功能。大量体外试验 数据表明，这些基质细胞生化地分化成细胞， 形态学上类似于成骨细胞。这些细胞在体内形成骨骼的能力 也进行了检查。该SBIR的第二阶段将扩展这些体内实验。 特异性目的1检查人脂肪组织来源的基质细胞的能力， 羟基磷灰石陶瓷块植入皮下形成异位骨， 免疫缺陷小鼠具体目标2探讨是否引入一个 修饰的骨形态发生蛋白受体将通过这些增强矿化 体外细胞具体目标3将确定这些改良的骨形态发生 表达蛋白质受体的基质细胞形成骨比 使用目标1中所述的体内鼠模型对对照细胞进行细胞培养。所有这些 研究将为大规模的临床前实验提供坚实的基础。 动物（犬）骨折修复模型。 拟定商业应用： 这项技术将提供一个具有成本效益的替代来源的基质细胞 能够分化成骨细胞用于自体和同种异体移植 植入骨缺损和骨折的部位这具有商业应用， 关节置换，骨折修复， 和继发于蛀牙的骨吸收。

Non-healing bone fractures and periodontal bone loss constitute significant clinical problems with few approved medical options. Bone repair is enhanced by the presence of osteoblasts or osteoblastic precursor cells. Subcutaneous adipose tissue is a plentiful, accessible, and replenishable source of human stromal cells for transplantation. In Phase I of this SBIR, we tested the hypothesis that human adipose tissue-derived stromal cells are capable of osteoblast function. Substantial in vitro data indicates that these stromal cells differentiate into cells biochemically and morphologically similar to osteoblasts. The ability of these cells to form bone in vivo was examined as well. Phase II of this SBIR will extend these in vivo experiments. Specific Aim 1 examines the ability of human adipose tissue-derived stromal cells to form ectopic bone in hydroxyapatite ceramic cubes implanted subcutaneously in immunodeficient mice. Specific Aim 2 explores whether the introduction of a modified bone morphogenetic protein receptor will enhance mineralization by these cells in vitro. Specific Aim 3 will determine if these modified bone morphogenetic protein receptor expressing stromal cells form bone more rapidly and efficiently than control cells using the in vivo murine model described in Aim 1. Together, these studies will provide a strong foundation for pre-clinical experiments in a large animal (canine) fracture repair model. PROPOSED COMMERCIAL APPLICATION: This technology will provide a cost-effective alternative source of stromal cells capable of osteoblast differentiation for autologous and allogeneic transplantation into sites of bone defects and fractures. This has commercial application to orthopedic and periodontal surgical treatments of joint replacement, fracture repair, and bone resorption secondary to tooth decay.