Spinal Fusion Using Adipose Derived Adult Stem Cells

描述(求职者提供)：超过75%的美国人在有生之年遭受背痛的折磨，每年有2%的美国劳动力在工作中背部受伤。脊柱融合术是治疗退行性腰椎间盘疾病、椎管狭窄、脊柱侧弯和脊柱骨折患者背部疼痛的常规矫形手术；然而，尽管机械固定设备的使用越来越多，但手术失败率在5%到44%之间，而且在过去20年中，成功率没有显著变化。再生医学通过将骨诱导生物材料和环境信号与成骨细胞相结合，通过促进异位新骨形成来改善和加速融合过程，为解决这一问题提供了一种新的途径。到目前为止，这项技术一直受到“现成成骨干细胞”可用性的限制。同源治疗公司在分离、培养和分化皮下脂肪组织中的成体干细胞方面拥有独特的知识产权和专业知识。我们已经证明这些脂肪来源的成体干细胞(ADAS)在体外和体内都具有成骨细胞的潜能。在这一科学背景下，我们假设：(A)ADAS细胞在体内是成骨的，与合适的生物材料载体相结合，将改善和加速动物模型的脊柱融合；(B)与生物材料支架相比，ADAS细胞可以与同种异体生物材料支架一起移植，实现更好的脊柱融合。本研究的第一阶段测试这些相互关联的假说的具体目的如下：目的1.确定同基因(Fischer大鼠来源)ADAS细胞对大鼠脊柱融合的影响。L4和L5脊柱间关节融合术将用于评估同种(Fischer大鼠来源)皮下ADAS细胞促进脊柱融合的成骨能力。目的2.确定同种异体(ACI大鼠来源)ADAS细胞在Fischer大鼠脊柱融合模型中的作用。目的3.比较同基因和同种异体ADAS细胞在脊柱融合模型中的相对有效性。这些第一阶段研究的结果将为研究人员在未来的第二阶段STTR中在大型动物模型中进行扩展的脊柱融合分析提供基础。用于临床整形外科手术的现成ADAS细胞的可用性将对商业和治疗产生重大影响。

DESCRIPTION (provided by applicant): Back pain afflicts over 75% of Americans during their lifetime and 2% of the American work force suffers a back injury on the job each year. Spinal fusion is the orthopedic procedure routinely used to treat back pain in patients suffering from degenerative disc disease, spinal stenosis, scoliosis, and spinal fracture; however, procedure failure rates range between 5 to 44% and the success rates have not changed significantly over the past 20 years despite increased use of mechanical fixation devices. Regenerative medicine offers a novel approach to this problem by combining osteoinductive biomaterials and environmental cues with osteogenic cells to improve and accelerate the fusion process by promoting ectopic new bone formation. So far, this technology has been limited by the availability of "off the shelf osteogenic stem cells. Cognate Therapeutics holds unique intellectual property and expertise in the isolation, culture, and differentiation of adult stem cells from subcutaneous adipose tissue. We have shown that these Adipose Derived Adult Stem (ADAS) cells display osteoblast potential both in vitro and in vivo. With this scientific background, we postulate: (A) That ADAS cells are osteogenic in vivo and, in combination with a suitable biomaterial carrier, will improve and accelerate spinal fusion in animal models and; (B) That ADAS cells can be transplanted allogeneically with a biomaterial scaffold to achieve a superior spinal fusion as compared to a biomaterial scaffold alone. This Phase I STTR tests these inter-related hypotheses with the following Specific Aims: Aim 1. To determine the effect of syngeneic (Fischer rat derived) ADAS cells on spinal fusion in a rat model. An intertransverse spinal arthrodesis (L4 and L5) will be used to evaluate the osteogenic ability of syngeneic (Fischer rat derived) subcutaneous ADAS cells to promote spinal fusion. Aim 2. To determine the effect of allogeneic (ACI rat derived) ADAS cells on spinal fusion in the Fischer rat model as outlined in Aim 1. Aim 3. To compare and contrast the relative effectiveness of syngeneic and allogeneic ADAS cells in a spinal fusion model. The results of these Phase I studies will provide the basis for an expanded spinal fusion analysis in a large animal model in a future Phase II STTR from the investigators. The availability of "off the shelf ADAS cells for clinical orthopedic procedures will have a significant commercial and therapeutic impact.