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Use of hESC-Derived Progenitors for the Treatment of Degenerated Discs

使用 hESC 衍生的祖细胞治疗退变椎间盘

基本信息

批准号：
9538353
负责人：
HICHAM M DRISSI
金额：
$ 17.16万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-16 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9538353
关键词：
Use hESC Derived Progenitors Treatment

项目摘要

DESCRIPTION (provided by applicant): There is no successful biologic treatment for degenerative disc disease. The overall goal of this application is to establish an optimal cell-based solution to disc degeneration. This objective stems from the multiple failed attempts to regenerate disc using adult mesenchymal stem cells in clinical trials. Thus, embryonic stem cell strategies bring novel possibilities to the treatment of disc-related back pain. Our current knowledge indicates that cells from the notochord, which are of embryonic origin, initiate the differentiation of mesenchymal progenitors into disc forming cells during the development of the spine as well as in early childhood. However, notochordal cells cannot be derived from adult stem cells. Therefore, we believe that embryonic progenitors are necessary to successfully derive disc-forming cells. Specifically, we propose to derive cellular components of the inner compartment of the intervertebral disc (nucleus pulposus) from human embryonic stem cells (H9 line) by generating mesenchymal-like stem cells and notochordal cells. Multiple ratios of these progenitors will be tested to form disc tissue components in vitro (Aim 1). The optimal ratio of hESC-derived notochordal and mesenchymal progenitor cells will be tested in a pre-clinical model of disc injury. Somatic cells will also be used as controls for the healing process (Aim 2). If successful, this high-risk proposal bears a strong potential to develop new and effective cell/matrix-based therapeutic strategies for the regeneration of human intervertebral discs.

描述（由申请人提供）：退行性椎间盘疾病尚无成功的生物治疗方法。该应用程序的总体目标是建立一种基于细胞的最佳椎间盘退变解决方案。这一目标源于在临床试验中使用成人间充质干细胞再生椎间盘的多次失败尝试。因此，胚胎干细胞策略为治疗椎间盘相关背痛带来了新的可能性。我们目前的知识表明，胚胎来源的脊索细胞在脊柱发育期间以及儿童早期启动间充质祖细胞分化为椎间盘形成细胞。然而，脊索细胞不能来自成体干细胞。因此，我们认为胚胎祖细胞是成功衍生椎间盘形成细胞所必需的。具体而言，我们建议从人胚胎干细胞（H9系）中产生间充质样干细胞和脊索细胞，从而获得椎间盘（髓核）内室的细胞成分。将测试这些祖细胞的多种比例以在体外形成椎间盘组织组分（目标1）。将在椎间盘损伤的临床前模型中测试hESC衍生的脊索和间充质祖细胞的最佳比例。体细胞也将被用作愈合过程的对照（目标2）。如果成功的话，这种高风险的提议具有很强的潜力，可以开发新的有效的基于细胞/基质的治疗策略，用于人类椎间盘的再生。