Spinal Fusion Using Adipose Derived Adult Stem Cells

背部疼痛困扰着超过75%的美国人，每年有2%的美国劳动力在工作中遭受背部损伤。脊柱融合术是常规用于治疗退行性椎间盘疾病、椎管狭窄、脊柱侧凸和脊柱骨折患者背痛的骨科手术;然而，手术失败率在5 - 44%之间，尽管机械固定器械的使用增加，但在过去20年中成功率没有显著变化。再生医学提供了一种新的方法来解决这个问题，通过结合骨诱导生物材料和环境线索与成骨细胞，以改善和加速融合过程，促进异位新骨形成。到目前为止，这项技术受到了“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，这些脂肪来源的成体干细胞（ADAS）在体外和体内显示成骨细胞的潜力。在这种科学背景下，我们假设：（A）ADAS细胞在体内是成骨的，并且与合适的生物材料载体组合将改善和加速动物模型中的脊柱融合;（B）ADAS细胞可以与生物材料支架同种异体移植，以实现与单独的生物材料支架相比上级的脊柱融合。本阶段I STTR测试这些相互关联的假设，具体目标如下：目标1。确定同基因（Fischer大鼠源性）ADAS细胞对大鼠模型脊柱融合的影响。将使用横突间脊柱关节固定术（L4和L5）评价同系（Fischer大鼠衍生）皮下ADAS细胞促进脊柱融合的成骨能力。目标2.如目的1所述，确定同种异体（ACI大鼠源性）ADAS细胞对Fischer大鼠模型中脊柱融合的影响。目标3。比较和对比同基因和同种异体ADAS细胞在脊柱融合模型中的相对有效性。这些I期研究的结果将为研究者在未来的II期STTR中在大型动物模型中进行扩展脊柱融合分析提供基础。用于临床骨科手术的现成ADAS细胞的可用性将具有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.