USE OF ADIPOSE-DERIVED PREADIPOCYTES IN BONE DISOREDERS

不可愈合的骨折和牙周骨丢失构成了重要的临床症状。 几乎没有得到批准的医疗选择的问题。骨修复通过以下方式增强 成骨细胞或成骨前体细胞的存在。皮下脂肪组织 是一种丰富的、可获得的、可补充的人类基质细胞来源，用于 移植。在这项SBIR的第一阶段，我们测试了人类脂肪的假设 组织来源的基质细胞具有成骨细胞功能。大量的体外实验 数据表明，这些基质细胞在生化上分化为细胞，并 在形态上与成骨细胞相似。这些细胞在体内形成骨的能力 也被检查过了。这项SBIR的第二阶段将延长这些活体实验。 特定目的1检查人类脂肪组织来源的基质细胞的能力 羟基磷灰石陶瓷块皮下植入形成异位骨 免疫缺陷小鼠。具体目标2探讨了引入 修饰的骨形态发生蛋白受体将通过这些促进矿化 体外培养的细胞。具体目标3将确定这些修饰的骨形态发生 表达蛋白质受体的基质细胞更快、更有效地形成骨 使用目标1中描述的体内小鼠模型控制细胞。总的来说，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。 建议的商业应用： 这项技术将提供一种具有成本效益的基质细胞替代来源 具有成骨细胞分化能力的自体和异体移植 骨缺损处和骨折处。这将在商业上应用于 骨科和牙周外科治疗关节置换，骨折修复， 和继发于龋齿的骨吸收。

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.