Induced pluripotent stem cell therapy for degenerated IVD

诱导多能干细胞治疗退化性 IVD

基本信息

批准号：
9891953
负责人：
Dmitriy Sheyn
金额：
$ 11.91万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9891953
关键词：
Acute Address Adult Animal Model Antiinflammatory Effect Area Attenuated Back Pain Biology Bone Tissue Cartilage Cell Survival Cell Therapy Cells Child Chronic Cicatrix Data Development Disease Dyes Educational workshop Embryonic Development Environment Family suidae Fibrosis Funding Gene Delivery Gene Expression Gene Expression Profiling Genetic Goals Harvest Histologic Human IL8 gene Image Imaging technology Immunoassay Immunology Inflammation Inflammatory Injections Injury Institute of Medicine (U.S.)Interferon Type II Interleukin-1 beta Interleukin-17 Interleukin-6 Intervertebral disc structure Knowledge Label Leadership Link Magnetic Resonance Imaging Measures Mentored Research Scientist Development Award Mentors Mentorship Methods Modeling Molecular Biology Monitor Musculoskeletal Natural regeneration Needles Organ Culture Techniques Outcome Study Pain Parents Pathogenesis Patients Peptides Phenotype Physiological Play Population Positioning Attribute Process Proteins Publications Puncture procedure Quantitative Reverse Transcriptase PCR Regenerative Medicine Rejuvenation Reporting Research Research Personnel Role Seasons Solid Source Supervision Symptoms TNF gene Techniques Testing Therapeutic Therapeutic Effect Tissue Engineering Training Training Programs Vertebral column Visit age related alternative treatment base career cell type cytokine design disc regeneration experience hands on research immunoregulation improved in vivo in vivo Model induced pluripotent stem cell innovation intervertebral disk degeneration notochord novel nucleus pulposus preclinical study quantitative imaging soft tissue stem cell therapy stem cells targeted treatment tissue regeneration transcriptome sequencing

项目摘要

Project Summary/abstract As many as 80% of the adult population experience back pain at some point in their lifetimes. Previous studies have indicated a link between back pain and intervertebral disc (IVD) degeneration in 40% of patients. Despite decades of research, robust therapies targeting underlying causes rather than symptoms are still in the earliest stages of development. Thus, there is an urgent need for alternative treatment, such as stem cell therapy, focused on correcting the underlying pathogenesis of DDD. Dr. Sheyn’s goal is to develop his academic career in musculoskeletal tissue engineering and stem cell therapy field, focusing on spine therapeutics. He has received excellent training in stem cell manipulation and gene delivery, in vivo models, bone tissue engineering and molecular biology. He has established solid track record of publications in the field and demonstrated strong capacity to conduct innovative research. The proposed training program is designed to build on Dr. Sheyn’s background and strengthen his expertise in specific areas most relevant to IVD therapeutics. Under the leadership and sponsorship of Dr. Clive Svendsen, the director of the Cedars-Sinai Regenerative Medicine Institute, Dr. Sheyn will gain experience in the three research areas: 1) development of soft tissue and cartilage biology; 2) immunology and inflammation; 3) quantitative imaging of soft tissue using magnetic resonance imaging (MRI). We will utilize formal workshops and courses and hands-on research supervised by seasoned mentors with extensive track record in these areas and mentorship to achieve those training goals. In the proposed study we will study the link between the possible mechanism of disc degeneration and the potential cell therapy. Firstly, we will investigate the developmental phenotype of novel induced pluripotent stem cell- derived notochordal cells as a potential source of cells to reverse the degeneration process and fibrosis of the disc. This aim will be conducted under mentorship of Dr. Lyons, well-established developmental and musculoskeletal biologist from UCLA and Dr. Hoyland, world expert in the notochord and IVD biology from Manchester U, UK. Secondly we will use the annular injury model of disc degeneration in pigs to study the role of pro-inflammatory and catabolic cytokines expressed by the NP cells under mentorship of Dr. Arditi, world known expert in immunology, inflammation and fibrosis., In Aim 3, the IVD degeneration will be assessed using MRI as shown in preliminary results, but also we will monitor the regeneration of the IVD using iPS-derived notochordal-like cells will be monitored under supervision of Dr. Li, world leader in MR research and imaging. Overall this study will improve our understanding of the disc degeneration and possible regeneration strategies, as well as will serve as excellent vehicle for Dr. Sheyn to strengthen his expertise in areas critical for addressing the DDD therapy and will place him in strong position to establish independent research to compete for substantial funding (R01).

项目概要/摘要先前的研究表明，多达 80% 的成年人在一生中的某个阶段会经历背痛。表明 40% 的患者背痛与椎间盘 (IVD) 退变之间存在联系。经过数十年的研究，最早的治疗方法仍然是针对根本原因而不是症状因此，迫切需要替代治疗，例如干细胞疗法， Sheyn 博士的目标是发展他的学术生涯。在肌肉骨骼组织工程和干细胞治疗领域，他专注于脊柱治疗。在干细胞操作和基因传递、体内模型、骨组织工程方面接受过良好的培训他在该领域建立了扎实的出版物记录并证明了这一点。拟议的培训计划旨在建立在博士的基础上。 Sheyn 的背景并增强了他在与 IVD 治疗最相关的特定领域的专业知识。 Cedars-Sinai 再生医学中心主任 Clive Svendsen 博士的领导和赞助 Sheyn博士将在研究所获得三个研究领域的经验：1）软组织和软骨的发育生物学；2) 免疫学和炎症；3) 使用磁共振进行软组织定量成像我们将利用正式的研讨会和课程以及由经验丰富的人监督的实践研究。在这些领域拥有丰富经验的导师，并为实现这些培训目标提供指导。拟议的研究我们将研究椎间盘退变的可能机制和潜在的之间的联系首先，我们将研究新型诱导多能干细胞的发育表型。衍生的脊索细胞作为逆转脊索退化过程和纤维化的潜在细胞来源这一目标将在 Lyons 博士的指导下进行，他具有完善的发展和加州大学洛杉矶分校的肌肉骨骼生物学家和来自美国的脊索和 IVD 生物学世界专家 Hoyland 博士其次，英国曼彻斯特大学将使用猪椎间盘退变的环形损伤模型来研究其作用。在 Arditi 博士的指导下，世界各地的 NP 细胞表达促炎和分解代谢细胞因子免疫学、炎症和纤维化领域的知名专家。在目标 3 中，将使用以下方法评估 IVD 变性：初步结果显示 MRI，但我们也将使用 iPS 衍生来监测 IVD 的再生脊索样细胞将在核磁共振研究和成像领域的世界领导者李博士的监督下进行监测。总的来说，这项研究将提高我们对椎间盘退变和可能的再生的理解战略，并将成为 Sheyn 博士加强关键领域专业知识的绝佳工具致力于解决 DDD 疗法，并将使他处于有利地位来建立独立研究竞争大量资金（R01）。