Spinal Fusion Using Adipose Derived Adult Stem Cells

描述（由申请人提供）：超过75%的美国人在其一生中遭受背部疼痛的折磨，每年有2%的美国劳动力在工作中遭受背部损伤。脊柱融合术是一种常规的骨科手术，用于治疗患有退行性椎间盘疾病、椎管狭窄、脊柱侧凸和脊柱骨折的患者的背痛；然而，手术失败率在5%到44%之间，在过去的20年里，尽管机械固定装置的使用越来越多，但成功率并没有明显变化。再生医学为解决这一问题提供了一种新的方法，将骨诱导生物材料和环境因素与成骨细胞结合起来，通过促进异位新骨的形成来改善和加速融合过程。到目前为止，这项技术受到“现成的成骨干细胞”的限制。Cognate Therapeutics在从皮下脂肪组织分离、培养和分化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，这些脂肪衍生成体干细胞（ADAS）在体外和体内都表现出成骨潜能。基于这一科学背景，我们假设：(A) ADAS细胞在体内具有成骨性，并且与合适的生物材料载体结合，将改善和加速动物模型中的脊柱融合；(B)与单独使用生物材料支架相比，ADAS细胞可以与生物材料支架异体移植以实现更好的脊柱融合。这个第一阶段的STTR测试这些相互关联的假设有以下具体目标：目的：探讨同基因（Fischer大鼠衍生）ADAS细胞对大鼠脊柱融合的影响。横断间腰椎融合术（L4和L5）将用于评估同基因（Fischer大鼠衍生）皮下ADAS细胞促进脊柱融合的成骨能力。目标2。在目的1中概述的Fischer大鼠模型中，确定同种异体（ACI大鼠衍生）ADAS细胞对脊柱融合的影响。目标3。比较和对比同基因和异体ADAS细胞在脊柱融合模型中的相对有效性。这些I期研究的结果将为研究者在未来的II期str中在大型动物模型中进行扩展的脊柱融合分析提供基础。“现成的ADAS细胞”在临床骨科手术中的可用性将产生重大的商业和治疗影响。

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.