Spinal Fusion Using Adipose Derived Adult Stem Cells

使用脂肪来源的成体干细胞进行脊柱融合

基本信息

批准号：
6928684
负责人：
Jeffrey Martin Gimble
金额：
$ 10万
依托单位：
COGNATE THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-16 至 2007-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6928684
关键词：
adipose tissue homologous transplantation laboratory rat nonhuman therapy evaluation osteoblasts osteogenesis spinal fusion stem cell transplantation stem cells therapy design /development

项目摘要

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.

描述（由申请人提供）：超过 75% 的美国人一生中都会遭受背痛的困扰，每年有 2% 的美国劳动力在工作中遭受背部伤害。脊柱融合术是一种常用于治疗椎间盘退行性疾病、椎管狭窄、脊柱侧凸和脊柱骨折患者背痛的矫形手术；然而，尽管机械固定装置的使用有所增加，但手术失败率在 5% 至 44% 之间，并且在过去 20 年中成功率没有显着变化。再生医学为解决这一问题提供了一种新方法，将骨诱导生物材料和环境因素与成骨细胞相结合，通过促进异位新骨形成来改善和加速融合过程。到目前为止，这项技术受到“现成成骨干细胞”可用性的限制。Cognate Therapeutics 在从皮下脂肪组织中分离、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) 在体外和体内都显示出成骨细胞的潜力，根据这一科学背景，我们假设：(A) ADAS 细胞在体内具有成骨作用，并且与合适的生物材料载体结合使用。改善和加速动物模型中的脊柱融合；（B）与单独的生物材料支架相比，ADAS 细胞可以与生物材料支架同种异体移植，以实现更好的脊柱融合。具体目标如下：目标 1. 确定同基因（Fischer 大鼠衍生）ADAS 细胞对大鼠模型中脊柱融合的影响，将使用横突间脊柱关节固定术（L4 和 L5）来实现。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. 如目标 1 中所述，确定同种异体（ACI 大鼠来源）ADAS 细胞对 Fischer 大鼠模型中脊柱融合的影响。目标 3. 比较和对比同种和同种异体 ADAS 细胞在脊柱融合中的相对有效性模型。这些第一阶段研究的结果将为研究人员在未来第二阶段 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”的可用性将产生重大的商业和治疗影响。